CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a division of U.S. patent application Ser. No. 09/749,637 filed 28 Dec. 2000. The present application is related to U.S. provisional patent application Ser. No. 60/173,754 filed 30 Dec. 1999, Ser. No. 60/214,263 filed 26 Jun. 2000, Ser. No. 60/219,440 filed 20 Jul. 2000 and Ser. No. 60/243,412 filed 27 Oct. 2000. Each of these applications is incorporated herein by reference.
This invention was made with Government support under Grant No. PO1 GM48677 awarded by the National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Md. The United States Government has certain rights in the invention.
BACKGROUND OF THE INVENTION The invention relates to relatively short peptides (termed O-Superfamily conotoxins herein), about 20-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include three disulfide bonds.
The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference, and for convenience are referenced in the following text by author and date and are listed alphabetically by author in the appended bibliography.
Conus is a genus of predatory marine gastropods (snails) which envenomate their prey. Venomous cone snails use a highly developed apparatus to deliver their cocktail of toxic conotoxins into their prey. In fish-eating species such as Conus magus the cone detects the presence of the fish using chemosensors in its siphon. When close enough the cone extends its proboscis and impales the fish with a hollow harpoon-like tooth containing venom. This immobilizes the fish and enables the cone snail to wind it into its mouth via the tooth held at the end of its proboscis. For general information on Conus and their venom see the web address grimwade.biochem.unimelb. edu.au/cone/referenc.html. Prey capture is accomplished through a sophisticated arsenal of peptides which target specific ion channel and receptor subtypes. Each Conus species venom appears to contain a unique set of 50-200 peptides. The composition of the venom differs greatly between species and between individual snails within each species, each optimally evolved to paralyze its prey. The active components of the venom are small peptide toxins, typically 10-30 amino acid residues in length and are typically highly constrained peptides due to their high density of disulphide bonds.
The venoms consist of a large number of different peptide components that when separated exhibit a range of biological activities: when injected into mice they elicit a range of physiological responses from shaking to depression. The paralytic components of the venom that have been the focus of recent investigation are the α, ω- and μ-conotoxins. All of these conotoxins act by preventing neuronal communication, but each targets a different aspect of the process to achieve this. The α-conotoxins target nicotinic ligand gated channels, the μ-conotoxins target the voltage-gated sodium channels and the ω-conotoxins target the voltage-gated calcium channels (Olivera et al., 1985; Olivera et al., 1990). For example a linkage has been established between α-, αA-& ψ-conotoxins and the nicotinic ligand-gated ion channel; ω-conotoxins and the voltage-gated calcium channel; μ-conotoxins and the voltage-gated sodium channel; δ-conotoxins and the voltage-gated sodium channel; κ-conotoxins and the voltage-gated potassium channel; conantokins and the ligand-gated glutamate (NMDA) channel. Five δ-conotoxins have been described: GmVIA (U.S. Pat. No. 5,719,264); PVIA (U.S. Pat. No. 5,739,276); TxVIA (Hillyard et al., 1989; Fainzilber et al., 1991); TxVIB (Fainzilber et al., 1991); NgVIA (Fainzilber et al., 1995); and TxIIA (Nakamura et al., 1996). For a partial list of Conus peptides and their amino acid sequences see the web address pir.georgetown.edu.
However, the structure and function of only a small minority of these peptides have been determined to date. For peptides where function has been determined, three classes of targets have been elucidated: voltage-gated ion channels; ligand-gated ion channels, and G-protein-linked receptors.
Conus peptides which target voltage-gated ion channels include those that delay the inactivation of sodium channels, as well as blockers specific for sodium channels, calcium channels and potassium channels. Peptides that target ligand-gated ion channels include antagonists of NMDA and serotonin receptors, as well as competitive and noncompetitive nicotinic receptor antagonists. Peptides which act on G-protein receptors include neurotensin and vasopressin receptor agonists. The unprecedented pharmaceutical selectivity of conotoxins is at least in part defined by a specific disulfide bond frameworks combined with hypervariable amino acids within disulfide loops (for a review see McIntosh et al., 1998).
Potassium channels comprise a large and diverse group of proteins that, through maintenance of the cellular membrane potential, are fundamental in normal biological function. These channels are vital in controlling the resting membrane potential in excitable cells and can be broadly sub-divided into three classes: voltage-gated K+ channels, Ca2+ activated K+ channels and ATP-sensitive K+ channels. Many disorders are associated with abnormal flow of potassium ions through these channels. The identification of agents which would regulate the flow of potassium ions through each of these channel types would be useful in treating disorders associated with such abnormal flow.
It is desired to identify additional conotoxin peptides having activities of the above conopeptides, as well as conotoxin peptides having additional activities.
SUMMARY OF THE INVENTION The invention relates to relatively short peptides (termed O-Superfamily conotoxins herein), about 20-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include three disulfide bonds. The O-superfamily conotoxins include ω-conotxins, κ-conotoxins, δ-conotoxins, μO-conotoxins and GS conotoxin.
Thus, in one embodiment, the present invention is directed to the conotoxin peptides set forth in Table 2 and the corresponding peptides set forth in Table 1.
In a second embodiment, the present invention is directed to all of the propeptides and nucleic acid sequences encoding the propeptides or peptides set forth in Table 1.
In a third embodiment, the present invention is directed to derivatives or pharmaceutically acceptable salts of the conotoxin peptides disclosed herein. Examples of derivatives include peptides in which the Arg residues may be substituted by Lys, ornithine, homoargine, nor-Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any synthetic basic amino acid; the Lys residues maybe substituted by Arg, ornithine, homoargine, nor-Lys, or any synthetic basic amino acid; the Tyr residues may be substituted with 125I-Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any synthetic hydroxy containing amino acid; the Ser residues may be substituted with Thr or any synthetic hydroxylated amino acid; the Thr residues may be substituted with Ser or any synthetic hydroxylated amino acid; the Phe residues may be substituted with any synthetic aromatic amino acid; the Trp residues may be substituted with Trp (D), neo-Trp, halo-Trp (D or L) or any aromatic synthetic amino acid; and the Asn, Ser, Thr or Hyp residues may be glycosylated. The halogen may be iodo, chloro, fluoro or bromo; preferably iodo for halogen substituted-Tyr and bromo for halogen-substituted Trp. The Tyr residues may also be substituted with the 3-hydroxyl or 2-hydroxylisomers (meta-Tyr or ortho-Tyr, respectively) and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic amino acid, e.g., tetrazolyl derivatives of Gly and Ala. The aliphatic amino acids may be substituted by synthetic derivatives bearing non-natural aliphatic branched or linear side chains CnH2n+2 up to and including n=8. The Leu residues may be substituted with Leu (D). The Glu residues may be substituted with Gla. The Gla residues may be substituted with Glu. The Met residues may be substituted with norleucine (Nle). The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L).
Examples of synthetic aromatic amino acid include, but are not limited to, nitro-Phe, 4-substituted-Phe wherein the substituent is C1-C3 alkyl, carboxyl, hyrdroxymethyl, sulphomethyl, halo, phenyl, —CHO, —CN, —SO3H and —NHAc. Examples of synthetic hydroxy containing amino acid, include, but are not limited to, such as 4-hydroxymethyl-Phe, 4-hydroxyphenyl-Gly, 2,6-dimethyl-Tyr and 5-amino-Tyr. Examples of synthetic basic amino acids include, but are not limited to, N-1-(2-pyrazolinyl)-Arg, 2-(4-piperidinyl)-Gly, 2-(4-piperidinyl)-Ala, 2-[3-(2S)pyrrolidininyl)-Gly and 2-[3-(2S)pyrrolidininyl)-Ala. These and other synthetic basic amino acids, synthetic hydroxy containing amino acids or synthetic aromatic amino acids are described in Building Block Index, Version 3.0 (1999 Catalog, pages 4-47 for hydroxy containing amino acids and aromatic amino acids and pages 66-87 for basic amino acids; see also web address amino-acids.com), incorporated herein by reference, by and available from RSP Amino Acid Analogues, Inc., Worcester, Mass. The residues containing protecting groups are deprotected using conventional techniques. Examples of synthetic acid amino acids include those derivatives bearing acidic functionality, including carboxyl, phosphate, sulfonate and synthetic tetrazolyl derivatives such as described by Omstein et al. (1993) and in U.S. Pat. No. 5,331,001, each incorporated herein by reference.
Optionally, in the peptides of the present invention, the Asn residues maybe modified to contain an N-glycan and the Ser, Thr and Hyp residues may be modified to contain an O-glycan (e.g., g-N, g-S, g-T and g-Hyp). In accordance with the present invention, a glycan shall mean any N-, S- or O-linked mono-, di-, tri-, poly- or oligosaccharide that can be attached to any hydroxy, amino or thiol group of natural or modified amino acids by synthetic or enzymatic methodologies known in the art. The monosaccharides making up the glycan can include D-allose, D-altrose, D-gluclose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-galactosamine, D-glucosamine, D-N-acetyl-glucosamine (GlcNAc), D-N-acetyl-galactosamine (GalNAc), D-fucose or D-arabinose. These saccharides may be structurally modified, e.g., with one or more O-sulfate, O-phosphate, O-acetyl or acidic groups, such as sialic acid, including combinations thereof. The gylcan may also include similar polyhydroxy groups, such as D-penicillamine 2,5 and halogenated derivatives thereof or polypropylene glycol derivatives. The glycosidic linkage is beta and 1-4 or 1-3, preferably 1-3. The linkage between the glycan and the amino acid may be alpha or beta, preferably alpha and is 1-.
Core O-glycans have been described by Van de Steen et al. (1998), incorporated herein by reference. Mucin type O-linked oligosaccharides are attached to Ser or Thr (or other hydroxylated residues of the present peptides) by a GalNAc residue. The monosaccharide building blocks and the linkage attached to this first GalNAc residue define the “core glycans,” of which eight have been identified. The type of glycosidic linkage (orientation and connectivities) are defined for each core glycan. Suitable glycans and glycan analogs are described further in U.S. Ser. No. 09/420,797 filed 19 Oct. 1999 (now U.S. Pat. No. 6,369,193) and in PCT Application No. PCT/US99/24380 filed 19 Oct. 1999 (PCT Published Application No. WO 00/23092), each incorporated herein by reference. A preferred glycan is Gal(β1→3)GalNAc(α1→).
Optionally, in the peptides of general formula I and the specific peptides described herein, pairs of Cys residues may be replaced pairwise with isoteric lactam or ester-thioether replacements, such as Ser/(Glu or Asp), Lys/(Glu or Asp), Cys/(Glu or Asp) or Cys/Ala combinations. Sequential coupling by known methods (Barnay et al., 2000; Hruby et al., 1994; Bitan et al., 1997) allows replacement of native Cys bridges with lactam bridges. Thioether analogs may be readily synthesized using halo-Ala residues commercially available from RSP Amino Acid Analogues.
The present invention is further directed to derivatives of the above peptides and peptide derivatives which are acylic permutations in which the cyclic permutants retain the native bridging pattern of native toxin. See, Craik et al. (2001).
In a fourth embodiment, the present invention is directed to uses of the conotoxin peptides described herein. In one aspect of this embodiment, members of the O-Superfamily conotoxins disclosed herein or a pharmaceutically acceptable salt or solvate thereof are used for regulating the flow of sodium ions through Na+ channels. Disorders which can be treated using these conopeptides include multiple sclerosis, other demyelinating diseases (such as acute dissenmiated encephalomyelitis, optic neuromyelitis, adrenoleukodystrophy, acute transverse myelitis, progressive multifocal leukoencephalopathy), sub-acute sclerosing panencephalomyelitis (SSPE), metachromatic leukodystrophy, Pelizaeus-Merzbacher disease, spinal cord injury, botulinum toxin poisoning, Huntington's chorea, compression and entrapment neurophathies (such as carpal tunnel syndrome, ulnar nerve palsy), cardiovascular disorders (such as cardiac arrhythmias, congestive heart failure), reactive gliosis, hyperglycemia, immunosuppression, cocaine addiction, cancer, cognitive dysfunction, disorders resulting from defects in neurotransmitter release (such as Eaton-Lambert syndrome), and reversal of the actions of curare and other neuromuscular blocking drugs.
In a second aspect of this embodiment, a method of treating disorders associated with voltage gated ion channel disorders in a subject is provided which comprises administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily contoxins described herein or a pharmaceutically acceptable salt or solvate thereof. Thus, these peptides can be used to treat neurologic disorders, such as anticonvulsant agents, or as neuroprotective agents, such as for treating stroke, or as cardiovascular agents or for the management of pain. These peptides can further be used to treat spasticity, spinal cord injury or upper motor neuron syndrome.
In a third aspect of this embodiment, a method of reducing/alleviating/decreasing the perception of pain by a subject or for inducing analgesia, particularly local analgesia, in a subject is provided which comprises administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily contoxins described herein or a pharmaceutically acceptable salt or solvate thereof.
In a fourth aspect of this embodiment, a method for activating (i.e., opening) ATP-sensitive K+ channels in a subject is provided which comprises administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily contoxins described herein or a pharmaceutically acceptable salt or solvate thereof.
In a fifth aspect of this embodiment, a method of treating disorders and conditions associated with proton-gated ion channels in a subject comprising administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily conotoxins described herein or a pharmaceutically acceptable salt or solvate thereof.
Another embodiment of the invention contemplates a method of identifying compounds that mimic the therapeutic activity of the instant peptide, comprising the steps of: (a) conducting a biological assay on a test compound to determine the therapeutic activity; and (b) comparing the results obtained from the biological assay of the test compound to the results obtained from the biological assay of the peptide. The peptide is labeled with any conventional label, preferably a radioiodine on an available Tyr. Thus, the invention is also directed to radioiodinated O-Superfamily conotoxins.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The invention relates to relatively short peptides (termed O-Superfamily conotoxins herein), about 20-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include three disulfide bonds.
The present invention, in another aspect, relates to a pharmaceutical composition comprising an effective amount of an O-Superfamily conotoxin peptide, a mutein thereof, an analog thereof, an active fragment thereof or pharmaceutically acceptable salts.
In one embodiment, such a pharmaceutical composition comprises a member of the O-Superfamily conotoxins described herein which has the capability of delaying inactivation of sodium channels. The activity of δ-conotoxin peptides, members of the O-Superfamily, on sodium channels is described in U.S. Pat. No. 5,739,276, incorporated herein by reference. The treatment of disorders according to this embodiment comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a pharmaceutical composition of the present invention.
Sodium channels comprise a large and diverse group of proteins that, through maintenance of the cellular membrane potential, are fundamental in normal biological function. The therapeutic applications for compounds that regulate the flow of sodium ions through Na+ channels are far-reaching and include treatments of a wide range of disease and injury states. Disorders which can be treated using these conopeptides include multiple sclerosis, other demyelinating diseases (such as acute dissenmiated encephalomyelitis, optic neuromyelitis, adrenoleukodystrophy, acute transverse myelitis, progressive multifocal leukoencephalopathy), sub-acute sclerosing panencephalomyelitis (SSPE), metachromatic leukodystrophy, Pelizaeus-Merzbacher disease, spinal cord injury, botulinum toxin poisoning, Huntington's chorea, compression and entrapment neurophathies (such as carpal tunnel syndrome, ulnar nerve palsy), cardiovascular disorders (such as cardiac arrhythmias, congestive heart failure), reactive gliosis, hyperglycemia, immunosuppression, cocaine addiction, cancer, cognitive dysfunction, disorders resulting from defects in neurotransmitter release (such as Eaton-Lambert syndrome), and reversal of the actions of curare and other neuromuscular blocking drugs.
In a second embodiment, such a pharmaceutical composition comprises a member of the O-Superfamily conotoxins described herein which has the capability of acting at voltage gated ion channels, particularly calcium channels, and are thus useful for treating a disorder or disease of a living animal body, including a human, which disorder or disease is responsive to the partial or complete blockade of voltage gated ion channels of the central nervous system. The activity of ω-conotoxin peptides, members of the O-Superfamily, on calcium channels is described in U.S. Pat. Nos. 5,587,454; 5,559,095 and 5,824,645, incorporated herein by reference. The treatment according to this embodiment comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a pharmaceutical composition of the present invention.
Voltage-gated calcium channels are present in neurons, and in cardiac, smooth, and skeletal muscle and other excitable cells, and are known to play a variety of roles in membrane excitability, muscle contraction, and cellular secretion, such as in synaptic transmission (McCleskey). In neuronal cells, voltage-gated calcium channels have been classified by their electrophysiological as well as by their biochemical (binding) properties. Six classes of physiologically distinct calcium channels have been identified to date, namely the T, L, N, P, Q, and R-type channels.
It is well known that an accumulation of calcium (calcium overload) in the brain is seen after anoxia, ischemia, migraine and other hyperactivity periods of the brain, such as after epileptic convulsions. An uncontrolled high concentration of calcium in the cells of the central nervous system (CNS) is known to cause most of the degenerative changes connected with the above diseases. Compounds which can block the calcium channels of brain cells are therefore useful in the treatment of stroke, anoxia, ischemia, migraine, psychosis, or epilepsy, any other convulsive disorder and in the prevention of the degenerative changes connected with the same.
Compounds blocking the so called L-type calcium channels in the CNS are useful for the treatment of the above disorders by directly blocking the calcium uptake in the CNS. Further, it is well known that the so called N- and P-types of calcium channels, as well as possibly other types of calcium channels, are involved in the regulation of neurotransmitter release. Compounds blocking the N- and/or P-types of calcium channels indirectly and very powerfully prevent calcium overload in the CNS after the hyperactivity periods of the brain as described above by inhibiting the enhanced neurotransmitter release seen after such hyperactivity periods of the CNS, and especially the neurotoxic, enhanced glutamate release after such hyperactivity periods of the CNS. Furthermore, blockers of the N- and/or P-types of calcium channels, as dependent upon the selectivity of the compound in question, inhibit the release of various other neurotransmitters such as aspartate, GABA, glycine, dopamine, serotonin and noradrenaline.
Thus, the pharmaceutical compositions comprising a member of the O-Superfamily conotoxins of the present invention are useful as neuroprotectants, cardiovascular agents, anticonvulsants, analgesics or adjuvants to general anesthetics. A “neurological disorder or disease” is a disorder or disease of the nervous system including, but not limited to, global and focal ischemic and hemorrhagic stroke, head trauma, spinal cord injury, hypoxia-induced nerve cell damage as in cardiac arrest or neonatal distress or epilepsy. In addition, a “neurological disorder or disease” is a disease state and condition in which a neuroprotectant, anticonvulsant, analgesic and/or as an adjunct in general anesthesia may be indicated, useful, recommended or prescribed.
More specifically, the present invention is directed to the use of a member of the O-Superfamily conotoxins for the treatment and alleviation of epilepsy and as a general anticonvulsant agent. The present invention is also directed to the use of these compounds for reducing neurotoxic injury associated with conditions of hypoxia, anoxia or ischemia which typically follows stroke, cerebrovascular accident, brain or spinal cord trauma, myocardial infarct, physical trauma, drowning, suffocation, perinatal asphyxia, or hypoglycemic events. The present invention is further directed to the use of O-superfamily-conotoxin peptides for treating pain, including acute and chronic pain, such migraine, nociceptive and neuropathic pain. These peptides can further be used to treat spasticity, spinal cord injury or upper motor neuron syndrome. Other uses of these compounds are described in U.S. Pat. No. 5,859,186, incorporated herein by reference.
A “neuroprotectant” is a compound capable of preventing the neuronal death associated with a neurological disorder or disease. An “anticonvulsant” is a compound capable of reducing convulsions produced by conditions such as simple partial seizures, complex partial seizures, status epilepticus, and trauma-induced seizures such as occur following head injury, including head surgery. An “analgesic” is a compound capable of relieving pain by altering perception of nociceptive stimuli without producing anesthesia or loss of consciousness. A “muscle relaxant” is a compound that reduces muscular tension. A “adjunct in general anesthesia” is a compound useful in conjunction with anesthetic agents in producing the loss of ability to perceive pain associated with the loss of consciousness.
The invention relates as well to methods useful for treatment of neurological disorders and diseases, including, but not limited to, global and focal ischemic and hemorrhagic stroke, head trauma, spinal cord injury, hypoxia-induced nerve cell damage such as in cardiac arrest or neonatal distress, epilepsy or other convulsive disorders without undesirable side effects.
Thus, in one aspect, the invention provides a method of reducing/alleviating/decreasing the perception of pain by a subject or for inducing analgesia in a subject comprising administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily conotoxins of the present invention or a pharmaceutically acceptable salt or solvate thereof. The pain may be acute, persistent, inflammatory or neuropathic pain.
In a second aspect, the invention provides a method of treating stroke, head or spinal cord trauma or injury, anoxia, hypoxia-induced nerve cell damage, ischemia, migraine, psychosis, anxiety, schizophrenia, inflammation, movement disorder, epilepsy, any other convulsive disorder or in the prevention of the degenerative changes connected with the same in a subject comprising administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily conotoxins of the present invention or a pharmaceutically acceptable salt or solvate thereof.
In a third embodiment, such a pharmaceutical composition comprises a member of the O-Superfamily conotoxins described herein which is useful as a local anesthetic for treating pain. These conopeptides have long lasting anesthetic activity and are particularly useful for spinal anesthesia, either administered acutely for post-operative pain or via an intrathecal pump for severe chronic pain situations or for treatment of pain in epithelial tissue. The activity of μO-conotoxin peptides, members of the O-Superfamily, on sodium channels is described in U.S. patent application Ser. No. 09/590,386 (International Application No. PCT/JUS00/15779) filed on 9 Jun. 2000, incorporated herein by reference. The treatment according to this embodiment comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a pharmaceutical composition of the present invention.
More specifically, in one aspect, the pain results from surgical or medical procedures, and a member of the O-Superfamily conotoxins as described herein is administered to the central nervous system (CNS), e.g. to the spine for spinal analgesia. In a second aspect, the pain is in an epithelial tissue region associated with damage or loss of epithelial tissue as a result of, for example, plastic surgery, canker sores, burns, sore throats, genital lesions, upper or lower gastrointestinal bronchoscopy or endoscopy, intubation, dermatologic abrasions or chemical skin peels, and a member of the O-Superfamily conotoxins as described herein is administered to alleviate the associated pain.
In a fourth embodiment, such a pharmaceutical composition comprises a member of the O-Superfamily conotoxins which has the capability of activating (i.e., opening) ATP-sensitive K+ channels, and is thus useful for for treating a disorder or disease of a living animal body, including a human, which disorder or disease is responsive to the activation of ATP-sensitive K+ channels. The activity of κ-conotoxin peptides, members of the O-Superfamily, on sodium channels is described in U.S. patent application Ser. No. 09/666,837 (International Application No. PCT/US00/25827) filed on 21 Sep. 2000, incorporated herein by reference. The treatment according to this embodiment comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a pharmaceutical composition of the present invention. Thus the invention provides a method for treating cardiac ischemia, neuronal ischemia, ocular ischemia or asthma in a subject comprising administering to the subject an effective amount of the pharmaceutical composition comprising a therapeutically effective amount of a member of the O-Superfamily conotoxins described herein or a pharmaceutically acceptable salt or solvate thereof.
In a fifth embodiment, such a pharmaceutical composition comprises a member of the O-Superfamily conotoxins which has the capability of acting on proton gated ion channels, and ise thus useful for treating a disorder, disease or condition of a living animal body, including a human, which disorder, disease or condition is responsive to the partial or complete blockade of proton-gated ion channels. Since, these members of the O-Superfamily antagonize the proton-gated ion channel, they are useful as analgesics, especially for pain associated with inflammation, hematomas, cardiac or muscle ischemia, or cancer. Thus, in one aspect of the present invention, the peptides and derivatives disclosed herein are useful as analgesics, i.e., for the reduction in the perception of pain or the induction of analgesia. The treatment according to this embodiment comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a pharmaceutical composition of the present invention.
The conotoxin peptides of the present invention are identified by isolation from Conus venom. Alternatively, the conotoxin peptides of the present invention are identified using recombinant DNA techniques by screening cDNA libraries of various Conus species using conventional techniques, such as the use of reverse-transcriptase polymerase chain reaction (RT-PCR) or the use of degenerate probes. Primers for RT-PCR are based on conserved sequences in the signal sequence and 3′ untranslated region of the conotoxin peptides genes isolated using degenerate probes. Clones which hybridize to degenerate probes are analyzed to identify those which meet minimal size requirements, i.e., clones having approximately 300 nucleotides (for a propeptide), as determined using PCR primers which flank the cDNA cloning sites for the specific cDNA library being examined. These minimal-sized clones and the clones produced by RT-PCR are then sequenced. The sequences are then examined for the presence of a peptide having the characteristics noted above for the O-Superfamily conotoxin peptides.
The conotoxin peptides described herein are sufficiently small to be chemically synthesized. General chemical syntheses for preparing the foregoing conotoxin peptides are described hereinafter. Various ones of the conotoxin peptides can also be obtained by isolation and purification from specific Conus species using the technique described in U.S. Pat. Nos. 4,447,356 (Olivera et al., 1984); 5,514,774; 5,719,264; and 5,591,821, as well as in PCT published application WO 98/03189, the disclosures of which are incorporated herein by reference.
Although the conotoxin peptides of the present invention can be obtained by purification from cone snails, because the amounts of conotoxin peptides obtainable from individual snails are very small, the desired substantially pure conotoxin peptides are best practically obtained in commercially valuable amounts by chemical synthesis using solid-phase strategy. For example, the yield from a single cone snail may be about 10 micrograms or less of conotoxin peptide. By “substantially pure” is meant that the peptide is present in the substantial absence of other biological molecules of the same type; it is preferably present in an amount of at least about 85% purity and preferably at least about 95% purity. Chemical synthesis of biologically active conotoxin peptides depends of course upon correct determination of the amino acid sequence.
The conotoxin peptides can also be produced by recombinant DNA techniques well known in the art. Such techniques are described by Sambrook et al. (1989). A gene of interest (i.e., a gene that encodes a suitable conotoxin peptide) can be inserted into a cloning site of a suitable expression vector by using standard techniques. These techniques are well known to those skilled in the art. The expression vector containing the gene of interest may then be used to transfect the desired cell line. Standard transfection techniques such as calcium phosphate co-precipitation, DEAE-dextran transfection or electroporation may be utilized. A wide variety of host/expression vector combinations may be used to express a gene encoding a conotoxin peptide of interest. Such combinations are well known to a skilled artisan. The peptides produced in this manner are isolated, reduced if necessary, and oxidized to form the correct disulfide bonds.
One method of forming disulfide bonds in the conotoxin peptides of the present invention is the air oxidation of the linear peptides for prolonged periods under cold room temperatures or at room temperature. This procedure results in the creation of a substantial amount of the bioactive, disulfide-linked peptides. The oxidized peptides are fractionated using reverse-phase high performance liquid chromatography (HPLC) or the like, to separate peptides having different linked configurations. Thereafter, either by comparing these fractions with the elution of the native material or by using a simple assay, the particular fraction having the correct linkage for maximum biological potency is easily determined. However, because of the dilution resulting from the presence of other fractions of less biopotency, a somewhat higher dosage may be required.
The peptides are synthesized by a suitable method, such as by exclusively solid-phase techniques, by partial solid-phase techniques, by fragment condensation or by classical solution couplings.
In conventional solution phase peptide synthesis, the peptide chain can be prepared by a series of coupling reactions in which constituent amino acids are added to the growing peptide chain in the desired sequence. Use of various coupling reagents, e.g., dicyclohexylcarbodiimide or diisopropylcarbonyldimidazole, various active esters, e.g., esters of N-hydroxyphthalimide or N-hydroxy-succinimide, and the various cleavage reagents, to carry out reaction in solution, with subsequent isolation and purification of intermediates, is well known classical peptide methodology. Classical solution synthesis is described in detail in the treatise, “Methoden der Organischen Chemie (Houben-Weyl): Synthese von Peptiden,” (1974). Techniques of exclusively solid-phase synthesis are set forth in the textbook, “Solid-Phase Peptide Synthesis,” (Stewart and Young, 1969), and are exemplified by the disclosure of U.S. Pat. No. 4,105,603 (Vale et al., 1978). The fragment condensation method of synthesis is exemplified in U.S. Pat. No. 3,972,859 (1976). Other available syntheses are exemplified by U.S. Pat. No. 3,842,067 (1974) and 3,862,925 (1975). The synthesis of peptides containing γ-carboxyglutamic acid residues is exemplified by Rivier et al. (1987), Nishiuchi et al. (1993) and Zhou et al. (1996).
Common to such chemical syntheses is the protection of the labile side chain groups of the various amino acid moieties with suitable protecting groups which will prevent a chemical reaction from occurring at that site until the group is ultimately removed. Usually also common is the protection of an α-amino group on an amino acid or a fragment while that entity reacts at the carboxyl group, followed by the selective removal of the α-amino protecting group to allow subsequent reaction to take place at that location. Accordingly, it is common that, as a step in such a synthesis, an intermediate compound is produced which includes each of the amino acid residues located in its desired sequence in the peptide chain with appropriate side-chain protecting groups linked to various ones of the residues having labile side chains.
As far as the selection of a side chain amino protecting group is concerned, generally one is chosen which is not removed during deprotection of the α-amino groups during the synthesis. However, for some amino acids, e.g., His, protection is not generally necessary. In selecting a particular side chain protecting group to be used in the synthesis of the peptides, the following general rules are followed: (a) the protecting group preferably retains its protecting properties and is not split off under coupling conditions, (b) the protecting group should be stable under the reaction conditions selected for removing the α-amino protecting group at each step of the synthesis, and (c) the side chain protecting group must be removable, upon the completion of the synthesis containing the desired amino acid sequence, under reaction conditions that will not undesirably alter the peptide chain.
It should be possible to prepare many, or even all, of these peptides using recombinant DNA technology. However, when peptides are not so prepared, they are preferably prepared using the Merrifield solid-phase synthesis, although other equivalent chemical syntheses known in the art can also be used as previously mentioned. Solid-phase synthesis is commenced from the C-terminus of the peptide by coupling a protected α-amino acid to a suitable resin. Such a starting material can be prepared by attaching an a-amino-protected amino acid by an ester linkage to a chloromethylated resin or a hydroxymethyl resin, or by an amide bond to a benzhydrylamine (BHA) resin or para-methylbenzhydrylamine (MBHA) resin. Preparation of the hydroxymethyl resin is described by Bodansky et al. (1966). Chloromethylated resins are commercially available from Bio Rad Laboratories (Richmond, Calif.) and from Lab. Systems, Inc. The preparation of such a resin is described by Stewart and Young (1969). BHA and MBHA resin supports are commercially available, and are generally used when the desired polypeptide being synthesized has an unsubstituted amide at the C-terminus. Thus, solid resin supports may be any of those known in the art, such as one having the formulae —O—CH2-resin support, —NH BHA resin support, or —NH-MBHA resin support. When the unsubstituted amide is desired, use of a BHA or MBHA resin is preferred, because cleavage directly gives the amide. In case the N-methyl amide is desired, it can be generated from an N-methyl BHA resin. Should other substituted amides be desired, the teaching of U.S. Pat. No. 4,569,967 (Kornreich et al., 1986) can be used, or should still other groups than the free acid be desired at the C-terminus, it may be preferable to synthesize the peptide using classical methods as set forth in the Houben-Weyl text (1974).
The C-terminal amino acid, protected by Boc or Fmoc and by a side-chain protecting group, if appropriate, can be first coupled to a chloromethylated resin according to the procedure set forth in K. Horiki et al. (1978), using KF in DMF at about 60° C. for 24 hours with stirring, when a peptide having free acid at the C-terminus is to be synthesized. Following the coupling of the BOC-protected amino acid to the resin support, the α-amino protecting group is removed, as by using trifluoroacetic acid (TFA) in methylene chloride or TFA alone. The deprotection is carried out at a temperature between about 0° C. and room temperature. Other standard cleaving reagents, such as HCl in dioxane, and conditions for removal of specific α-amino protecting groups may be used as described in Schroder & Lubke (1965).
After removal of the α-amino-protecting group, the remaining α-amino- and side chain-protected amino acids are coupled step-wise in the desired order to obtain the intermediate compound defined hereinbefore, or as an alternative to adding each amino acid separately in the synthesis, some of them may be coupled to one another prior to addition to the solid phase reactor. Selection of an appropriate coupling reagent is within the skill of the art. Particularly suitable as a coupling reagent is N,N′-dicyclohexylcarbodiimide (DCC, DIC, HBTU, HATU, TBTU in the presence of HOBt or HOAt).
The activating reagents used in the solid phase synthesis of the peptides are well known in the peptide art. Examples of suitable activating reagents are carbodiimides, such as N,N′-diisopropylcarbodiimide and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide. Other activating reagents and their use in peptide coupling are described by Schroder & Lubke (1965) and Kapoor (1970).
Each protected amino acid or amino acid sequence is introduced into the solid-phase reactor in about a twofold or more excess, and the coupling may be carried out in a medium of dimethylformamide (DMF):CH2Cl2 (1:1) or in DMF or CH2Cl2 alone. In cases where intermediate coupling occurs, the coupling procedure is repeated before removal of the α-amino protecting group prior to the coupling of the next amino acid. The success of the coupling reaction at each stage of the synthesis, if performed manually, is preferably monitored by the ninhydrin reaction, as described by Kaiser et al. (1970). Coupling reactions can be performed automatically, as on a Beckman 990 automatic synthesizer, using a program such as that reported in Rivier et al. (1978).
After the desired amino acid sequence has been completed, the intermediate peptide can be removed from the resin support by treatment with a reagent, such as liquid hydrogen fluoride or TFA (if using Fmoc chemistry), which not only cleaves the peptide from the resin but also cleaves all remaining side chain protecting groups and also the α-amino protecting group at the N-terminus if it was not previously removed to obtain the peptide in the form of the free acid. If Met is present in the sequence, the Boc protecting group is preferably first removed using trifluoroacetic acid (TFA)/ethanedithio]prior to cleaving the peptide from the resin with HF to eliminate potential S-alkylation. When using hydrogen fluoride or TFA for cleaving, one or more scavengers such as anisole, cresol, dimethyl sulfide and methylethyl sulfide are included in the reaction vessel.
Cyclization of the linear peptide is preferably affected, as opposed to cyclizing the peptide while a part of the peptido-resin, to create bonds between Cys residues. To effect such a disulfide cyclizing linkage, fully protected peptide can be cleaved from a hydroxymethylated resin or a chloromethylated resin support by ammonolysis, as is well known in the art, to yield the fully protected amide intermediate, which is thereafter suitably cyclized and deprotected. Alternatively, deprotection, as well as cleavage of the peptide from the above resins or a benzhydrylamine (BHA) resin or a methylbenzhydrylamine (MBHA), can take place at 0° C. with hydrofluoric acid (HF) or TFA, followed by oxidation as described above.
The peptides are also synthesized using an automatic synthesizer. Amino acids are sequentially coupled to an MBHA Rink resin (typically 100 mg of resin) beginning at the C-terminus using an Advanced Chemtech 357 Automatic Peptide Synthesizer. Couplings are carried out using 1,3-diisopropylcarbodimide in N-methylpyrrolidinone (NMP) or by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and diethylisopro-pylethylamine (DIEA). The FMOC protecting group is removed by treatment with a 20% solution of piperidine in dimethylformamide (DMF). Resins are subsequently washed with DMF (twice), followed by methanol and NMP.
Muteins, analogs or active fragments, of the foregoing tconotoxin peptides are also contemplated here. See, e.g., Hammerland et al, Eur. J. Pharmacol., 226, pp. 239-244 (1992). Derivative muteins, analogs or active fragments of the conotoxin peptides may be synthesized according to known techniques, including conservative amino acid substitutions, such as outlined in U.S. Pat. Nos. 5,545,723 (see particularly col. 2, line 50—col. 3, line 8); 5,534,615 (see particularly col. 19, line 45—col. 22, line 33); and 5,364,769 (see particularly col. 4, line 55—col. 7, line 26), each herein incorporated by reference.
Pharmaceutical compositions containing a compound of the present invention or its pharmaceutically acceptable salts or solvates as the active ingredient can be prepared according to conventional pharmaceutical compounding techniques. See, for example, Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack Publishing Co., Easton, Pa.). Typically, an antagonistic amount of the active ingredient will be admixed with a pharmaceutically acceptable carrier. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., intravenous, oral or parenteral. The compositions may further contain antioxidizing agents, stabilizing agents, preservatives and the like. For examples of delivery methods see U.S. Pat. No. 5,844,077, incorporated herein by reference.
“Pharmaceutical composition” means physically discrete coherent portions suitable for medical administration. “Pharmaceutical composition in dosage unit form” means physically discrete coherent units suitable for medical administration, each containing a daily dose or a multiple (up to four times) or a sub-multiple (down to a fortieth) of a daily dose of the active compound in association with a carrier and/or enclosed within an envelope. Whether the composition contains a daily dose, or for example, a half, a third or a quarter of a daily dose, will depend on whether the pharmaceutical composition is to be administered once or, for example, twice, three times or four times a day, respectively.
The term “salt”, as used herein, denotes acidic and/or basic salts, formed with inorganic or organic acids and/or bases, preferably basic salts. While pharmaceutically acceptable salts are preferred, particularly when employing the compounds of the invention as medicaments, other salts find utility, for example, in processing these compounds, or where non-medicament-type uses are contemplated. Salts of these compounds may be prepared by art-recognized techniques.
Examples of such pharmaceutically acceptable salts include, but are not limited to, inorganic and organic addition salts, such as hydrochloride, sulphates, nitrates or phosphates and acetates, trifluoroacetates, propionates, succinates, benzoates, citrates, tartrates, fumarates, maleates, methane-sulfonates, isothionates, theophylline acetates, salicylates, respectively, or the like. Lower alkyl quaternary ammonium salts and the like are suitable, as well.
As used herein, the term “pharmaceutically acceptable” carrier means a non-toxic, inert solid, semi-solid liquid filler, diluent, encapsulating material, formulation auxiliary of any type, or simply a sterile aqueous medium, such as saline. Some examples of the materials that can serve as pharmaceutically acceptable carriers are sugars, such as lactose, glucose and sucrose, starches such as corn starch and potato starch, cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt, gelatin, talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol, polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate, agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline, Ringer's solution; ethyl alcohol and phosphate buffer solutions, as well as other non-toxic compatible substances used in pharmaceutical formulations.
Wetting agents, emulsifiers and lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. Examples of pharmaceutically acceptable antioxidants include, but are not limited to, water soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfite, sodium metabisulfite, sodium sulfite, and the like; oil soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, aloha-tocopherol and the like; and the metal chelating agents such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid and the like.
For oral administration, the compounds can be formulated into solid or liquid preparations such as capsules, pills, tablets, lozenges, melts, powders, suspensions or emulsions. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, suspending agents, and the like in the case of oral liquid preparations (such as, for example, suspensions, elixirs and solutions); or carriers such as starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like in the case of oral solid preparations (such as, for example, powders, capsules and tablets). Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar-coated or enteric-coated by standard techniques. The active agent can be encapsulated to make it stable to passage through the gastrointestinal tract while at the same time allowing for passage across the blood brain barrier. See for example, WO 96/11698.
For parenteral administration, the compound may be dissolved in a pharmaceutical carrier and administered as either a solution or a suspension. Illustrative of suitable carriers are water, saline, dextrose solutions, fructose solutions, ethanol, or oils of animal, vegetative or synthetic origin. The carrier may also contain other ingredients, for example, preservatives, suspending agents, solubilizing agents, buffers and the like. When the compounds are being administered intrathecally, they may also be dissolved in cerebrospinal fluid.
A variety of administration routes are available. The particular mode selected will depend of course, upon the particular drug selected, the severity of the disease state being treated and the dosage required for therapeutic efficacy. The methods of this invention, generally speaking, may be practiced using any mode of administration that is medically acceptable, meaning any mode that produces effective levels of the active compounds without causing clinically unacceptable adverse effects. Such modes of administration include oral, rectal, sublingual, topical, nasal, transdermal or parenteral routes. The term “parenteral” includes subcutaneous, intravenous, epidural, irrigation, intramuscular, release pumps, or infusion.
For example, administration of the active agent according to this invention may be achieved using any suitable delivery means, including:
-
- (a) pump (see, e.g., Luer & Hatton (1993), Zimm et al. (1984) and Ettinger et al. (1978));
- (b), microencapsulation (see, e.g., U.S. Pat. Nos. 4,352,883; 4,353,888; and 5,084,350);
- (c) continuous release polymer implants (see, e.g., U.S. Pat. No. 4,883,666);
- (d) macroencapsulation (see, e.g., U.S. Pat. Nos. 5,284,761, 5,158,881, 4,976,859 and 4,968,733 and published PCT patent applications WO92/19195, WO 95/05452);
- (e) naked or unencapsulated cell grafts to the CNS (see, e.g., U.S. Pat. Nos. 5,082,670 and 5,618,531);
- (f) injection, either subcutaneously, intravenously, intra-arterially, intramuscularly, or to other suitable site; or
- (g) oral administration, in capsule, liquid, tablet, pill, or prolonged release formulation.
In one embodiment of this invention, an active agent is delivered directly into the CNS, preferably to the brain ventricles, brain parenchyma, the intrathecal space or other suitable CNS location, most preferably intrathecally. This administration is preferably by a pump.
Alternatively, targeting therapies may be used to deliver the active agent more specifically to certain types of cell, by the use of targeting systems such as antibodies or cell specific ligands. Targeting may be desirable for a variety of reasons, e.g. if the agent is unacceptably toxic, or if it would otherwise require too high a dosage, or if it would not otherwise be able to enter the target cells.
The active agents, which are peptides, can also be administered in a cell based delivery system in which a DNA sequence encoding an active agent is introduced into cells designed for implantation in the body of the patient, especially in the spinal cord region. Suitable delivery systems are described in U.S. Pat. No. 5,550,050 and published PCT Application Nos. WO 92/19195, WO 94/25503, WO 95/01203, WO 95/05452, WO 96/02286, WO 96/02646, WO 96/40871, WO 96/40959 and WO 97/12635. Suitable DNA sequences can be prepared synthetically for each active agent on the basis of the developed sequences and the known genetic code.
The active agent is preferably administered in a therapeutically effective amount. By a “therapeutically effective amount” or simply “effective amount” of an active compound is meant a sufficient amount of the compound to treat the desired condition at a reasonable benefit/risk ratio applicable to any medical treatment. The actual amount administered, and the rate and time-course of administration, will depend on the nature and severity of the condition being treated. Prescription of treatment, e.g. decisions on dosage, timing, etc., is within the responsibility of general practitioners or specialists, and typically takes account of the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of techniques and protocols can be found in Remington's Pharmaceutical Sciences.
Dosage may be adjusted appropriately to achieve desired drug levels, locally or systemically. Typically the active agents of the present invention exhibit their effect at a dosage range from about 0.001 mg/kg to about 250 mg/kg, preferably from about 0.01 mg/kg to about 100 mg/kg of the active ingredient, more preferably from a bout 0.05 mg/kg to about 75 mg/kg. A suitable dose can be administered in multiple sub-doses per day. Typically, a dose or sub-dose may contain from about 0.1 mg to about 500 mg of the active ingredient per unit dosage form. A more preferred dosage will contain from about 0.5 mg to about 100 mg of active ingredient per unit dosage form. Dosages are generally initiated at lower levels and increased until desired effects are achieved. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. Continuous dosing over, for example 24 hours or multiple doses per day are contemplated to achieve appropriate systemic levels of compounds.
For the treatment of pain, if the route of administration is directly to the CNS, the dosage contemplated is from about 1 ng to about 100 mg per day, preferably from about 100 ng to about 10 mg per day, more preferably from about 1 μg to about 100 μg per day. If administered peripherally, the dosage contemplated is somewhat higher, from about 100 ng to about 1000 mg per day, preferably from about 10 μg to about 100 mg per day, more preferably from about 100 μg to about 10 mg per day. If the conopeptide is delivered by continuous infusion (e.g., by pump delivery, biodegradable polymer delivery or cell-based delivery), then a lower dosage is contemplated than for bolus delivery.
Advantageously, the compositions are formulated as dosage units, each unit being adapted to supply a fixed dose of active ingredients. Tablets, coated tablets, capsules, ampoules and suppositories are examples of dosage forms according to the invention.
It is only necessary that the active ingredient constitute an effective amount, i.e., such that a suitable effective dosage will be consistent with the dosage form employed in single or multiple unit doses. The exact individual dosages, as well as daily dosages, are determined according to standard medical principles under the direction of a physician or veterinarian for use humans or animals.
The pharmaceutical compositions will generally contain from about 0.0001 to 99 wt. %, preferably about 0.001 to 50 wt. %, more preferably about 0.01 to 10 wt. % of the active ingredient by weight of the total composition. In addition to the active agent, the pharmaceutical compositions and medicaments can also contain other pharmaceutically active compounds. Examples of other pharmaceutically active compounds include, but are not limited to, analgesic agents, cytokines and therapeutic agents in all of the major areas of clinical medicine. When used with other pharmaceutically active compounds, the conotoxin peptides of the present invention may be delivered in the form of drug cocktails. A cocktail is a mixture of any one of the compounds useful with this invention with another drug or agent. In this embodiment, a common administration vehicle (e.g., pill, tablet, implant, pump, injectable solution, etc.) would contain both the instant composition in combination supplementary potentiating agent. The individual drugs of the cocktail are each administered in therapeutically effective amounts. A therapeutically effective amount will be determined by the parameters described above; but, in any event, is that amount which establishes a level of the drugs in the area of body where the drugs are required for a period of time which is effective in attaining the desired effects.
The practice of the present invention employs, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA, genetics, immunology, cell biology, cell culture and transgenic biology, which are within the skill of the art. See, e.g., Maniatis et al., 1982; Sambrook et al., 1989; Ausubel et al., 1992; Glover, 1985; Anand, 1992; Guthrie and Fink, 1991; Harlow and Lane, 1988; Jakoby and Pastan, 1979; Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins eds. 1984); Transcription And Translation (B. D. Hames & S. J. Higgins eds. 1984); Culture Of Animal Cells (R. I. Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells And Enzymes (IRL Press, 1986); B. Perbal, A Practical Guide To Molecular Cloning (1984); the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); Gene Transfer Vectors For Mammalian Cells (J. H. Miller and M. P. Calos eds., 1987, Cold Spring Harbor Laboratory); Methods In Enzymology, Vols. 154 and 155 (Wu et al. eds.), Immunochemical Methods In Cell And Molecular Biology (Mayer and Walker, eds., Academic Press, London, 1987); Handbook Of Experimental Immunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986); Riott, Essential Immunology, 6th Edition, Blackwell Scientific Publications, Oxford, 1988; Hogan et al., Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986).
EXAMPLES The present invention is described by reference to the following Examples, which are offered by way of illustration and are not intended to limit the invention in any manner. Standard techniques well known in the art or the techniques specifically described below were utilized.
EXAMPLE 1 Isoation of O-Superfamily Conotoxins Crude venom was extracted from venom ducts (Cruz et al., 1976), and the components were purified as previously described (Cartier et al., 1996). The crude extract from venom ducts was purified by reverse phase liquid chromatography (RPLC) using a Vydac C18 semi-preparative column (10×250 mm). Further purification of bioactive peaks was done on a Vydac C18 analytical column (4.6×220 mm). The effluents were monitored at 220 nm. Peaks were collected, and aliquots were assayed for activity.
The amino acid sequence of the purified peptides were determined by standard methods. The purified peptides were reduced and alkylated prior to sequencing by automated Edman degradation on an Applied Biosystems 477A Protein Sequencer with a 120A Analyzer (DNA/Peptide Facility, University of Utah) (Martinez et al., 1995; Shon et al., 1994).
In accordance with this method, peptides δ-GmVIA, δ-PVIA, δ-SVIE, δ-SVIE [DIE], δ-NgVIA, δ-TxVIA and Israel TxVIA were obtained.
EXAMPLE 2 Synthesis of Conopeptides The synthesis of conopeptides, either the mature toxins or the precursor peptides, was separately performed using conventional protection chemistry as described by Cartier et al. (1996). Briefly, the linear chains were built on Rink amide resin by Fmoc procedures with 2-(1H-benzotriol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborated coupling using an ABI model 430A peptide sythesizer with amino acid derivatives purchased from Bachem (Torrence Calif.). Orthogonal protection was used on cysteines: two cysteines were protected as the stable Cys(S-acetamidomethyl), while the other two cysteines were protected as the acid-labile Cys(S-trityl). After removal of the terminal Fmoc protecting group and cleavage of the peptides from the resins, the released peptides were precipitated by filtering the reaction mixture into −10° C. methyl t-butyl ether, which removed the protecting groups except the Cys(S-acetamidomethyl). The peptides were dissolved in 0.1% TFA and 60% acetonitrile and purified by RPLC on a Vydac C18 preparative column (22×250 mm) and eluted at a flow rate of 20 mL/min with a gradient of acetonitrile in 0.1% TFA.
The disulfide bridges in the three conopeptides were formed as described in Cartier et al. (1996). Briefly, the disulfide bridges between one pair of cysteines were formed by air oxidation which was judged to be complete by analytical RPLC. The monocyclic peptides were purified by RPLC on a Vydac C18 prepartive column (22×250 mm) and eluted with a gradient of acetonitrile in 0.1% TFA. Removal of S-acetamidomethyl groups and closure of the disulfide bridge between the other pair of cysteines was carried out simultaneously be iodine oxidation. The cyclic peptides were purified by RPLC on a Vydac C18 prepartive column (22×250 mm) and eluted with a gradient of acetonitrile in 0.1% TFA.
EXAMPLE 3 Isolation of DNA Encoding O-Superfamily Conotoxins DNA coding for conotoxins described herein was isolated and cloned in accordance with conventional techniques using general procedures well known in the art, such as described in Olivera et al. (1996). Alternatively, cDNA libraries was prepared from Conus venom duct using conventional techniques. DNA from single clones was amplified by conventional techniques using primers which correspond approximately to the M13 universal priming site and the M13 reverse universal priming site. Clones having a size of approximately 300-500 nucleotides were sequenced and screened for similarity in sequence to known O-Superfamily conotoxins, including the 6-conotoxins isolated in Example 1. The DNA sequences, encoded propeptide sequences and sequences of the mature toxins are set forth in the attached Table 1. DNA sequences coding for the mature toxin can also be prepared on the basis of the DNA sequences set forth on these pages. An alignment of the conotoxins is set forth in Table 2. TABLE 1
Sequences of Mature O-Superfamily Conotoxins,
Propeptides and DNA Encoding Propeptides
Name: δ-GmVIA
Species: gloriamaris
Isolated: Yes
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:1)
GTCACGGCTGATGACTCCGGAAATGGAATGGAGATTCTTTTTCCGAAGGCGGGTCA
CGAAATGGAGAACCTCGAAGTCTCTAATCGGGTCAAGCCGTGCCGTAAAGAAGGTC
AACTTTGTGATCCGATATTTCAAAACTGCTGCCGTGGCTGGAATTGCGTTCTTTTCTG
CGTCTGAAACTACCGTGATGTCTTCTCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSGNGMEILFPKAGHEMENLEVSNRVKPCRKEGQ (SEQ ID NO:2)
LCDPIFQNCCRGWNCVLFCV
Toxin Sequence:
Val-Lys-Xaa3-Cys-Arg-Lys-Xaa1-Gly-Gln-Leu-Cys-Asp-Xaa3-Ile-Phe-Gln-Asn-Cys-Cys-Arg- (SEQ ID NO:3)
Gly-Xaa4-Asn-Cys-Val-Leu-Phe-Cys-Val-{circumflex over ( )}
Name: δ-GmVIA [F15Y]
Species: gloriamaris
Toxin Sequence:
Val-Lys-Xaa3-Cys-Arg-Lys-Xaa1-Gly-Gln-Leu-Cys-Asp-Xaa3-Ile-Xaa5-Gln-Asn-Cys-Cys-Arg- (SEQ ID NO:4)
Gly-Xaa4-Asn-Cys-Val-Leu-Phe-Cys-Val-{circumflex over ( )}
Name: δ-GmVIA [F27Y]
Species: gloriamaris
Isolated: No
Toxin Sequence:
Val-Lys-Xaa3-Cys-Arg-Lys-Xaa1-Gly-Gln-Leu-Cys-Asp-Xaa3-Ile-Phe-Gln-Asn-Cys-Cys-Arg- (SEQ ID NO:5)
Gly-Xaa4-Asn-Cys-Val-Leu-Xaa5-Cys-Val-{circumflex over ( )}
Name: Omaria9
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
GAAGCTGGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATCA (SEQ ID NO:6)
TCGATCCATCTGTCCATCCATCCATTCATTCATTCGCTGCCAGACTATAATAAACATT
CAAGTCTCTCTTTCTTTTTGTGTCTGACAGATCGATCAGGATGTGCCGTAGAGAAGC
TCAACTTTGTGATCCGATTTTTCAAAACTGCTGCCATGGCTTGTTTTGCGTTTTGGTC
TGCGTCTAAAACTACCGTGATGTCTTCTCCTCCCCTCTAGTAGTAGTAGGCGGCCGC
TCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTATAGTG
TCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCT
GGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAAT
AGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGA
ATGGGACGCGCCCTGTAGCGGCGCATTAT
Translation:
SIRMCRREAQLCDPIFQNCCHGLFCVLVCV (SEQ ID NO:7)
Toxin Sequence:
Met-Cys-Arg-Arg-Xaa1-Ala-Gln-Leu-Cys-Asp-Xaa3-Ile-Phe-Gln-Asn-Cys-Cys-His-Gly-Leu- (SEQ ID NO:8)
Phe-Cys-Val-Leu-Val-Cys-Val-{circumflex over ( )}
Name: Tx6.11
Species: textile
Isolated: No
Cloned: Yes
DNA Sequence:
GGCATTACCTAAAACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGT (SEQ ID NO:9)
GCTGTTCTTGACCGCCTGGACATTCGTCACGGCTGATGACTCCAGAAATGGAATGGA
GAATCTTTTTCCGAAGGCAGGTCACGAAATGGAGAACCTCGAAGACTCTAAACACA
GGCACCAGGAGAGACCGGACACCGGCGACAAAGAAGAGATGCTGCTACAGAGACA
GGTCAAGCCGTGTCGTAAAGAACATCAACTTTGTGATCTGATTTTTCAAAACTGCTG
CCGTGGCTGGTATTGCGTTGTTCTGTCTTGCACTTGAAAGCTACCTGATGTGTTCTAC
TCCCATC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRNGMENLFPKAGHEMENLEDSKHRHQERPDTG (SEQ ID NO:10)
DKEEMLLQRQVKPCRKEHQLCDLIFQNCCRGWYCVVLSCT
Toxin Sequence:
Xaa2-Val-Lys-Xaa3-Cys-Arg-Lys-Xaa1-His-Gln-Leu-Cys-Asp-Leu-Ile-Phe-Gln-Asn-Cys-Cys- (SEQ ID NO:11)
Arg-Gly-Xaa4-Xaa5-Cys-Val-Val-Leu-Ser-Cys-Thr-{circumflex over ( )}
Name: Om6.6
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCGTTGCCGTGCTGTCCTTGACCGGCTGGACATTC (SEQ ID NO:12)
GTCACGGCTGATGACTCTGGAAATGGATTGGGGAATCTTTTTTCGAATGCACATCAC
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCGTTCCACACGAGGG
CCCTTGTAATTGGCTTACACAAAACTGCTGCAGTGGTTATAATTGCATCATTTTTTTC
TGCCTATAAAACTACCGTGATGTCTTCTCTTCCCCTC
Translation:
MKLTCLMIVAVLSLTGWTFVTADDSGNGLGNLFSNAHHEMKNPEASKLNKRCVPHEGP (SEQ ID NO:13)
CNWLTQNCCSGYNCIIFFCL
Toxin Sequence:
Cys-Val-Xaa3-His-Xaa1-Gly-Xaa3-Cys-Asn-Xaa4-Leu-Thr-Gln-Asn-Cys-Cys-Ser-Gly-Xaa5- (SEQ ID NO:14)
Asn-Cys-Ile-Ile-Phe-Phe-Cys-Leu-{circumflex over ( )}
Name: Da6.2
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGCTGATCATTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:15)
GTCACGGCTGATGACTCCGGAAATGGAATGGAGAATCTTTTTCCGAAGGCACGTCA
CGAAATGGAGAACCTCGAAGACTCTAAACACAGGCACCAGGAGAGACCGGACACG
GGCGACAAAGAAGAGATGCTGCTACAGAGACAGGTCAAGCCGTGTCGTAAAGAAC
ATCAACTTTGTGATCTGATTTTTCAAAACTGCTGCCGTGGCTGGTATTGCTTGCTTCG
TCCTTGCATCTGAAACTACCGTGATGTCTTCTCTCCCATC
Translation:
MKLTCLLIIAVLFLTAWTFVTADDSGNGMENLFPKARHEMENLEDSKHRHQERPDTGD (SEQ ID NO:16)
KEEMLLQRQVKPCRKEHQLCDLIFQNCCRGWYCLLRPCI
Toxin Sequence:
Xaa2-Val-Lys-Xaa3-Cys-Arg-Lys-Xaa1-His-Gln-Leu-Cys-Asp-Leu-IIe-Phe-Gln-Asn-Cys-Cys- (SEQ ID NO:17)
Arg-Gly-Xaa4-Xaa5-Cys-Leu-Leu-Arg-Xaa3-Cys-Ile-{circumflex over ( )}
Name: Da6.6
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTATGCTGATCATTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:18)
GTCACGGCTGATGACTCCGGAAATGGAATGGAGAATCTTTTTCCGAAGGCACGTCA
CGAAATGGAGAACCTCGAAGACTCTAAACACAGGCACCAGGAGAGACCGGACACG
GGCGACAAAGAAGAGATGCTGCTACAGAGACGGGTCAAGCCGTGCAGTGAAGAAG
GTCAACTTTGTGATCCACTTTCTCAAAACTGCTGCCGTGGCTGGCATTGCGTTCTTGT
CTCTTGCGTCTGAAACTACCGTGATGTCTTCTCTCCCATC
Translation:
MKLTCMLIIAVLFLTAWTFVTADDSGNGMENLFPKARHEMENLEDSKHRHQERPDTGD (SEQ ID NO:19)
KEEMLLQRRVKPCSEEGQLCDPLSQNCCRGWHCVLVSCV
Toxin Sequence:
Val-Lys-Xaa3-Cys-Ser-Xaa1-Xaa1-Gly-Gln-Leu-Cys-Asp-Xaa3-Leu-Ser-Gln-Asn-Cys-Cys- (SEQ ID NO:20)
Arg-Gly-Xaa4-His-Cys-Val-Leu-Val-Ser-Cys-Val-{circumflex over ( )}
Name: δ-TxVIA
Species: textile
Isolated: Yes
Cloned: Yes
DNA Sequence:
AAACATCGCCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGAC (SEQ ID NO:21)
CGCCTGGACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTC
GAATGCACATCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGGT
GCAAACAAAGCGGTGAAATGTGTAATTTGTTAGACCAAAACTGCTGCGACGGCTAT
TGCATAGTACTTGTCTGCACATAAAACTGCCGTGATGTCTTCTCTTCCCCTCTGTGCT
ACCTGGCTTGATCTTTGATTGGCGCGTGTCGTTCACTGGTTATGAACCCCCCCCCCC
CCCCCCCCCCCCCCCTTCCGGCTCTCTGGAGGCCTCGGGGGTTCAACATCCAAATAA
AGTGACAG
Translation:
MKLTCMMIVAVLFLTAWTFATADDPRNGLGNLFSNAHHEMKNPEASKLNKRWCKQSG (SEQ ID NO:22)
EMCNLLDQNCCDGYCIVLVCT
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp-Gly- (SEQ ID NO:23)
Xaa5-Cys-Ile-Val-Leu-Val-Cys-Thr-{circumflex over ( )}
Name: δ-TxVIA [M8J]
Species: textile
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Xaa6-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp-Gly- (SEQ ID NO:24)
Xaa5-Cys-Ile-Val-Leu-Val-Cys-Thr-{circumflex over ( )}
Name: M6.4
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:25)
GCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTCGAATGCACATCAC
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGGTGCAAACAAAGCG
GTGAAATGTGTAATTTGTTAGACCAAAACTGCTGCGACGGCTATTGCATAGTACTTG
TCTGCACATAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLGNLFSNAHHEMKNPEASKLNKRWCKQSG (SEQ ID NO:26)
EMCNLLDQNCCDGYCIVLVCT
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp-Gly- (SEQ ID NO:27)
Xaa5-Cys-Ile-Val-Leu-Val-Cys-Thr-{circumflex over ( )}
Name: Israel TxIA
Species: textile
Isolated: Yes
Cloned: No
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp-Gly- (SEQ ID NO:28)
Xaa5-Cys-Ile-Val-Phe-Val-Cys-Thr-{circumflex over ( )}
Name: Di6.2
Species: distans
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:29)
GCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTCGAATGCACATCAC
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGGTGCAAACAAAGCG
GTGAAATGTGTAATTTGTTAGACCAAAACTGCTGCGACGGCTATTGCATAGTACTTG
TCTGCACATAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCLMIVAVLFLTAWTFATADDPRNGLGNLFSNAHHEMKNPEASKLNKRWCKQSG (SEQ ID NO:30)
EMCNLLDQNCCDGYCIVLVCT
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp-Gly- (SEQ ID NO:31)
Xaa5-Cys-Ile-Val-Leu-Val-Cys-Thr-{circumflex over ( )}
Name: Af6.9
Species: ammiralis
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:32)
GCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTCGAATGCACATCAC
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGGTGCAAACAAAGCG
GTGAAATGTGTAATTTGTTAGACCAAAACTGCTGCGAGGGCTATTGCATAGTACTTG
TCTGCACATAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLGNLFSNAHHEMKNPEASKLNKRWCKQSG (SEQ ID NO:33)
EMCNLLDQNCCEGYCIVLVCT
Toxin Sequence:
Xaa4-Cys-Lys-Gln-Ser-Gly-Xaa1-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Xaa1-Gly- (SEQ ID NO:34)
Xaa5-Cys-Ile-Val-Leu-Val-Cys-Thr-{circumflex over ( )}
Name: Da6.4
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:35)
GCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTTTTGAAGGCACATCA
CGAAATGAACCCCGAAGCCTCTAAGTTGAATGAGAGGTGCCTTGGTGGTGGTGAAG
TTTGTGATATCTTTTTTCCACAATGCTGTGGCTATTGCATTCTTCTTTTCTGCACATAA
AACTACCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLENLFLKAHHEMNPEASKLNERCLGGGEVC (SEQ ID NO:36)
DIFFPQCCGYCILLFCT
Toxin Sequence:
Cys-Leu-Gly-Gly-Gly-Xaa1-Val-Cys-Asp-Ile-Phe-Phe-Xaa3-Gln-Cys-Cys-Gly-Xaa5-Cys-Ile- (SEQ ID NO:37)
Leu-Leu-Phe-Cys-Thr-{circumflex over ( )}
Name: Gm6.5
Species: gloriamaris
Isolated: No
Cloned: Yes
DNA Sequence:
GCTTGCACGGTGAATTTGGCTTCACAGTTTTCCACTGTCGTCTTTGGCATCATCTGAA (SEQ ID NO:38)
ACATCGCCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCG
CCTGGACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGGGAATATTTTTTCGA
ATGCACATCACGAAATGAAGAATCCCGAAGCCTCTAAATTGAACAAGAGGTGCCGT
CTAGGGGCTGAAAGTTGTGATGTAATTTCACAAAACTGCTGCCAAGGCACGTGCGT
TTTTTTCTGCTTACCATGATGTCTTCTATTCTCCTCTGTGCTACCTGGCTTGATCTTTC
ATTAGCGCGTGCCTTTCACTGGTTATGAACCCCCTGATCCGACTCTCTGGCAGCCTC
GGGGGTTCAACATCCAAATAAAACGACAGCACAATGACAAA
Translation:
MKLTCMMIVAVLFLTAWTFATADDPRNGLGNIFSNAHHEMKNPEASKLNKRCRLGAES (SEQ ID NO:39)
CDVISQNCCQGTCVFFCLP
Toxin Sequence:
Cys-Arg-Leu-Gly-Ala-Xaa1-Ser-Cys-Asp-Val-Ile-Ser-Gln-Asn-Cys-Cys-Gln-Gly-Thr-Cys-Val- (SEQ ID NO:40)
Phe-Phe-Cys-Leu-Leu-Xaa3-{circumflex over ( )}
Name: Gm6.6
Species: gloriamaris
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCTTGCACGGTGAATTTGGCTTCACAGTTTTCCACTGTCGTCTTTCGCATCATC (SEQ ID NO:41)
CAAAACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTG
ACCGCCTGGACATTCGCCACGGCTGATGACCCCAGAAATGGATTGGAGAAACTTTT
TTCGAATACACATCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGT
GCAAACAAGCTGATGAATCTTGTAATGTATTTTCACTTGACTGCTGCACCGGCTTAT
GCTTGGGATTCTGCGTATCGTGATGTCTTCTACTCCCCTCTGTgCTACCTGGCTTGAT
CTTTGATTGGCGTGTGCCTTTCATTGGTTATGAACCCCCCTGATCCGATTCTTTGGCG
GCCTCGGGGGTTCAACATCCAAATAAAGCGACAGCACAATAAAAAA
Translation:
MKLTCMMIVAVLFLTAWTFATADDPRNGLEKLFSNTHHEMKNPEASKLNKRCKQADE (SEQ ID NO:42)
SCNVFSLDCCTGLCLGFCVS
Toxin Sequence:
Cys-Lys-Gln-Ala-Asp-Xaa1-Ser-Cys-Asn-Val-Phe-Ser-Leu-Asp-Cys-Cys-Thr-Gly-Leu-Cys- (SEQ ID NO:43)
Leu-Gly-Phe-Cys-Val-Ser-{circumflex over ( )}
Name: Gm6.3
Species: gloriamaris
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCACCTGGACATTC (SEQ ID NO:44)
GCCACGGCCATCACCAGGAATGGATTGGGGAATCTTTTTCCGAAGAATCATCACGA
AATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCGTTCCATACGAGGGCC
CTTGTAATTGGCTTACACAAAACTGCTGCGATGAGCTATGCGTATTTTTCTGCCTAT
AAAACTAGCCTGATGT
Translation:
MKLTCMMIVAVLFLTTWTFATAITRNGLGNLFPKNHHEMKNPEASKLNKRCVPYEGPC (SEQ ID NO:45)
NWLTQNCCDELCVFFCL
Toxin Sequence:
Cys-Val-Xaa3-Xaa5-Xaa1-Gly-Xaa3-Cys-Asn-Xaa4-Leu-Thr-Gln-Asn-Cys-Cys-Asp-Xaa1-Leu- (SEQ ID NO:46)
Cys-Val-Phe-Phe-Cys-Leu-{circumflex over ( )}
Name: M6.5
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTCTTCTTGACCGTCTGGACATTC (SEQ ID NO:47)
GCCACGGCTGATGACTCCGGAAATGGATTGGAGAAACTTTTTTCGAATGCACATCA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCAAACAAGCTGAT
GAACCTTGTGATGTATTTTCACTTGAATGCTGCACCGGCATATGTCTTGGATTCTGC
ACGTGGTGATGTCTTCCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTVWTFATADDSGNGLEKLFSNAHHEMKNPEASKLNKRCKQADE (SEQ ID NO:48)
PCDVFSLECCTGICLGFCTW
Toxin Sequence:
Cys-Lys-Gln-Ala-Asp-Xaa1-Xaa3-Cys-Asp-Val-Phe-Ser-Leu-Xaa1-Cys-Cys-Thr-Gly-Ile-Cys (SEQ ID NO:49)
Leu-Gly-Phe-Cys-Thr-Xaa4-{circumflex over ( )}
Name: Tx6.2
Species: textile
Isolated: No
Cloned: Yes
DNA Sequence:
GCCTTGCACGGTGAATTTGGCTTCATAGTTTTCCACTGTCGTCTTTGGCATCATCCAA (SEQ ID NO:50)
AACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACC
GCCTGGACATTCGCCACGGCTGATGACTCCAGCAATGGATTGGAGAATCTTTTTTTG
AAGGCACATCACGAAATGAACCCCGAAGCCTCTAAGTTGAACGAGAGGTGCCTTGA
TGCTGGTGAAGTTTGTGATATTTTTTTTCCAACATGCTGCGGCTATTGCATTCTTCTT
TTCTGCGCATAAAACTACCGTGATGTCTTCTACTCCCCTCTGTGCTACCTGGCTTGAT
CTTTGATTGGCGCGTACCCTTCACTGGTTATGAAACCCCTGATCCAGCTCTCTGGAG
GCCTCGGGGGTTCAACATCCAAATAAAGCGACA
Translation:
MKLTCMMIVAVLFLTAWTFATADDSSNGLENLFLKAHHEMNPEASKLNERCLDAGEV (SEQ ID NO:51)
CDIFFPTCCGYCILLFCA
Toxin Sequence:
Cys-Leu-Asp-Ala-Gly-Xaa1-Val-Cys-Asp-Ile-Phe-Phe-Xaa3-Thr-Cys-Cys-Gly-Xaa5-Cys-Ile- (SEQ ID NO:52)
Leu-Leu-Phe-Cys-Ala-{circumflex over ( )}
Name: KK-1
Species: textile
Toxin Sequence:
Cys-Ile-Xaa1-Gln-Phe-Asp-Xaa3-Cys-Xaa1-Met-Ile-Arg-His-Thr-Cys-Cys-Val-Gly-Val-Cys- (SEQ ID NO:53)
Phe-Leu-Met-Ala-Cys-Ile-{circumflex over ( )}
Name: KK-2
Species: textile
Toxin Sequence:
Cys-Ala-Xaa3-Phe-Leu-His-Xaa3-Cys-Thr-Phe-Phe-Phe-Xaa3-Asn-Cys-Cys-Asn-Ser-Xaa5- (SEQ ID NO:54)
Cys-Val-Gln-Phe-Ile-Cys-Leu-{circumflex over ( )}
Name: Om6.1
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:55)
GCCACGGCTGATGACCCCAGAAATGGATTGGAGAATTTTTTTTCGAAGACACAACA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCCTAGCAGAACATG
AAACTTGTAATATATTTACACAAAACTGCTGCGAAGGCGTGTGCATTTTTATCTGCG
TACAAGCTCCAGAGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFATADDPRNGLEMTSKTQHEMKNPEASKLNKRCLAEHET (SEQ ID NO:56)
CNIFTQNCCEGVCIFICVQAPE
Toxin Sequence:
Cys-Leu-Ala-Xaa1-His-Xaa1-Thr-Cys-Asn-Ile-Phe-Thr-Gln-Asn-Cys-Cys-Xaa1-Gly-Val-Cys- (SEQ ID NO:57)
Ile-Phe-Ile-Cys-Val-Gln-Ala-Xaa3-Xaa1-{circumflex over ( )}
Name: Om6.3
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACTGTCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:58)
GCCACGGCTGAAGACCCCAGACATGGATTGGAGAATCTTTTTTCGAAGGCACATCA
CGAAATGAAGAACCCTGAAGACTCTAAATTGGACAAGAGGTGCATTCCACATTTTG
ACCCTTGTGACCCGATACGCCACACCTGCTGCTTTGGCCTGTGCCTACTAATAGCCT
GCATCTAAAACTGCCGTGATGTCTTCTCTCCCATC
Translation:
MKLTVMMIVAVLFLTAWTFATAEDPRHGLENLFSKAHHEMKNPEDSKLDKRCIPHFDP (SEQ ID NO:59)
CDPIRHTCCFGLCLLIACI
Toxin Sequence:
Cys-Ile-Xaa3-His-Phe-Asp-Xaa3-Cys-Asp-Xaa3-Ile-Arg-His-Thr-Cys-Cys-Phe-Gly-Leu-Cys- (SEQ ID NO:60)
Leu-Leu-Ile-Ala-Cys-Ile-{circumflex over ( )}
Name: Om6.4
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGACCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:61)
GTCACGGCTGAAGACCCCAGAGATGGATTGAAGAATCTTTTATCAAATGCACATAA
CGAAATGAAGAACCCCGAAGCCTCTACATTGAACGAGAGGTGCCTTGGGTTTGGTG
AAGCTTGTCTTATACTTTATTCAGACTGCTGCGGCTATTGCGTTGGTGCTATCTGCCT
ATAAAACTACCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMTVAVLFLTAWTFVTAEDPRDGLKNLLSNAHNEMKNPEASTLNERCLGFGE (SEQ ID NO:62)
ACLILYSDCCGYCVGAICL
Toxin Sequence:
Cys-Leu-Gly-Phe-Gly-Xaa1-Ala-Cys-Leu-Ile-Leu-Xaa5-Ser-Asp-Cys-Cys-Gly-Xaa5-Cys-Val- (SEQ ID NO:63)
Gly-Ala-Ile-Cys-Leu-{circumflex over ( )}
Name: Au6.1
Species: aulicus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:64)
GCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTTTCGAAGACACAACA
CAAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCAAAGCAGAAAAT
GAACTTTGTAATATATTTATACAAAACTGCTGCGACGGGACGTGCCTTCTTATCTGC
ATACAAAATCCACAGTGATGTCTTCTCTCCTACCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLENLFSKTQHKMKNPEASKLNKRCKAENE (SEQ ID NO:65)
LCNIFIQNCCDGTCLLICIQNPQ
Toxin Sequence:
Cys-Lys-Ala-Xaa1-Asn-Xaa1-Leu-Cys-Asn-Ile-Phe-Ile-Gln-Asn-Cys-Cys-Asp-Gly-Thr-Cys- (SEQ ID NO:66)
Leu-Leu-Ile-Cys-Ile-Gln-Asn-Xaa3-Gln-{circumflex over ( )}
Name: Au6.2
Species: aulicus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:67)
GCCACGGCTGATGACCCCAGAAATGGATTGGATAATCGTTTTTCGAAGGCACGTCA
CGAAATGAATAACCGCAGAGCCTCTAAATTGAACAAGAGGTGCCTTGAGTTTGGTG
AACTTTGTAATTTTTTTTTCCCAACCTGCTGCGGCTATTGCGTTCTTCTTGTCTGCCTA
TAAACTACCGTGATGTCTTCTCTTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLDNRFSKARHEMNNRRASKLNKRCLEFGE (SEQ ID NO:68)
LCNFFFPTCCGYCVLLVCL
Toxin Sequence:
Cys-Leu-Xaa1-Phe-Gly-Xaa1-Leu-Cys-Asn-Phe-Phe-Phe-Xaa3-Thr-Cys-Cys-Gly-Xaa5-Cys- (SEQ ID NO:69)
Val-Leu-Leu-Val-Cys-Leu-{circumflex over ( )}
Name: Da6.5
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:70)
GTCATGGCTGATGACTCCGGAAATGGATTGGAAAATCTGTTTTCGAAGGCACATCA
CGAAATGAAGAACCCTGAAGCCTCTAAATTGAACAAGAGGTGCGCTCAAAGCAGTG
AATTATGTGATGCGCTGGACTCAGACTGCTGCAGTGGTGTTTGCATGGTATTTTTCT
GCCTATAAAACTGCCGTGATGTCTTCTCTATCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFVMADDSGNGLENLFSKAHHEMKNPEASKLNKRCAQSSE (SEQ ID NO:71)
LCDALDSDCCSGVCMVFFCL
Toxin Sequence:
Cys-Ala-Gln-Ser-Ser-Xaa1-Leu-Cys-Asp-Ala-Leu-Asp-Ser-Asp-Cys-Cys-Ser-Gly-Val-Cys-Met- (SEQ ID NO:72)
Val-Phe-Phe-Cys-Leu-{circumflex over ( )}
Name: Di6.4
Species: distans
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGACCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:73)
GTCACGGCTGAAGACCCCAGAGATGGATTGAGGAATCTTTTATCGAATGCACGTCA
TGAAATGAAGAACCCCGAAGCCTCTAAATTGAACGAGAGGTGCCTTGGGTTTGGTG
AAGCTTGTCTTATGCTTTATTCAGACTGCTGCAGCTATTGCGTTGGTGCTGTCTGCCT
ATAAAACTACCGTGATGTCTTCTACTCCCATC
Translation:
MKLTCVMTVAVLFLTAWTFVTAEDPRDGLRNLLSNARHEMKNPEASKLNERCLGFGE (SEQ ID NO:74)
ACLMLYSDCCSYCVGAVCL
Toxin Sequence:
Cys-Leu-Gly-Phe-Gly-Xaa1-Ala-Cys-Leu-Met-Leu-Xaa5-Ser-Asp-Cys-Cys-Ser-Xaa5-Cys-Val- (SEQ ID NO:75)
Gly-Ala-Val-Cys-Leu-{circumflex over ( )}
Name: Pn6.2
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGACCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:76)
GCCACGGCTGAAGACCCCAGAAATGGATTGGAGAATCTTTTTTCGAAGGCACATCA
CGAAATGAAGAACCCTGAAGACTCTAAATTGGACAAGAGGTGCGTTAAATATCTTG
ACCCTTGTGACATGTTACGCCACACCTGCTGCTTTGGCCTGTGCGTACTAATAGCCT
GCATCTAAAACTGCCGTGATGTCTTCTACTCCCATC
Translation:
MKLTCLMTVAVLFLTAWTFATAEDPRNGLENLFSKAHHEMKNPEDSKLDKRCVKYLD (SEQ ID NO:77)
PCDMLRHTCCFGLCVLIACI
Toxin Sequence:
Cys-Val-Lys-Xaa5-Leu-Asp-Xaa3-Cys-Asp-Met-Leu-Arg-His-Thr-Cys-Cys-Phe-Gly-Leu-Cys- (SEQ ID NO:78)
Val-Leu-Ile-Ala-Cys-Ile-{circumflex over ( )}
Name: Pn6.3
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:79)
GCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTCGAATGCACATCAC
GAAATGAAGAACCCCGAAGCTTCTAAATTGAACGAGAGGTGCCTTGGGTTTGGTGA
AGTTTGCAATTTCTTTTTTCCAAACTGCTGCAGCTATTGCGTTGCTCTTGTCTGCCTA
TAAAACTACCGTGATGTCTTCTATTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFATADDPRNGLGNLFSNAHHEMKNPEASKLNERCLGFGEV (SEQ ID NO:80)
CNFFFPNCCSYCVALVCL
Toxin Sequence:
Cys-Leu-Gly-Phe-Gly-Xaa1-Val-Cys-Asn-Phe-Phe-Phe-Xaa3-Asn-Cys-Cys-Ser-Xaa5-Cys-Val- (SEQ ID NO:81)
Ala-Leu-Val-Cys-Leu-{circumflex over ( )}
Name: Pn6.4
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGCTCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:82)
GCCACGGCTGATGACTCCAGCAATGGACTGGAGAATCTTTTTTCGAAGGCACATCA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCATTCCACAATTTG
ATCCTTGTGACATGGTACGTCACACTTGCTGCAAAGGGTTGTGCGTACTAATAGCCT
GCTCTAAAACTGCGTGATGTCTTCATCTCCCCTC
Translation:
MKLTCVMLVAVLFLTAWTFATADDSSNGLENLFSKAHHEMKNPEASKLNKRCIPQFDP (SEQ ID NO:83)
CDMVRHTCCKGLCVLIACSKTA
Toxin Sequence:
Cys-Ile-Xaa3-Gln-Phe-Asp-Xaa3-Cys-Asp-Met-Val-Arg-His-Thr-Cys-Cys-Lys-Gly-Leu-Cys- (SEQ ID NO:84)
Val-Leu-Ile-Ala-Cys-Ser-Lys-Thr-Ala-{circumflex over ( )}
Name: Pn6.7
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCTTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:85)
GCCACGGCTGATGACCCCAGAAATGGATTGGAGAATTTTTTTTCGAAGACACAACA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCAAAGCAGAAAGT
GAAGCTTGTAATATAATTACACAAAACTGCTGCGACGGCAAGTGCCTTTTTTTCTGC
ATACAAATTCCAGAGTGATGTCTTCTCCTCCCATC
Translation:
MKLTCLMIVAVLFLTAWTFATADDPRNGLENFFSKTQHEMKNPEASKLNKRCKAESEA (SEQ ID NO:86)
CNIITQNCCDGKCLFFCIQIPE
Toxin Sequence:
Cys-Lys-Ala-Xaa1-Ser-Xaa1-Ala-Cys-Asn-Ile-Ile-Thr-Gln-Asn-Cys-Cys-Asp-Gly-Lys-Cys-Leu- (SEQ ID NO:87)
Phe-Phe-Cys-Ile-Gln-Ile-Xaa3-Xaa1-{circumflex over ( )}
Name: Omaria3
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
GGTCGACATCATCATCATCATCGATCCATCTGTCCATCCATCCATTCATTCATTCGCT (SEQ ID NO:88)
GCCAGACTGTCATAAATATTCGAGTCTCTCCTTCTGTTTGTATCTGACAGATTGAAC
AAGAGGTGCATTGACGGTGGTGAAATTTGTGATATTTTTTTTCCAAACTGCTGCAGT
GGGTGGTGCATTATTCTCGTCTGCGCATGAAACTACCGTGATGTCTTCTACTCCCCTC
TAGTAGTAGTAGGCGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGA
CGTCATAGCTCTTCTATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAAC
GTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCC
CTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCAACAGT
TTGCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGC
GGGTGTGGTGGGTaCGCGCAGCGTGACCGGTACACTTGCCAGCGCCCTAGCGCCCGC
TCCTTTTGCTTTCTTCCCTTCCTTTCTCGCCACCGTTCgCCCGGGGTTTTCCCGTCaAG
CTC
Translation:
LNKRCIDGGEICDIFFPNCCSGWCIILVCA (SEQ ID NO:89)
Toxin Sequence:
Cys-Ile-Asp-Gly-Gly-Xaa1-Ile-Cys-Asp-Ile-Phe-Phe-Xaa3-Asn-Cys-Cys-Ser-Gly-Xaa4-Cys- (SEQ ID NO:90)
Ile-Leu-Val-Cys-Ala-{circumflex over ( )}
Name: Omaria1
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
GGTCGACATCATCATCATCGATCCATCTGTCCATCCATCCATTCATTCATTCGCTGCC (SEQ ID NO:91)
AGACTGTCATAAATATTCGAGTCTCTCCTTCTGTTTGTATCTGACAGATTGAACAAG
AGGTGCCTTGACGGTGGTGAAATTTGTGGTATTTTGTTTCCAAGCTGCTGCAGTGGG
TGGTGCATTGTTCTCGTCTGCGCATGAAACTACCGTGATGTCTTCTACTCCCCTCTAG
TAGTAGTAGGCGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGT
CATAGCTCTTCTATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTC
GTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTT
TCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAAGTT
GCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGG
GTGTGGTGGTTACGCGCACCGTGACCGCTACACTTGCCAGCGCCCTAGCCGCCCGCT
CCTTTCGCTTTCTTCCCTTcCTTTCTCGCACGTTCGGCCGGCTTTCCCCGTCAAGCTCT
AAATCGGGGGCTTCCCTTTTA
Translation:
LNKRCLDGGEICGILFPSCCSGWCIVLVCA (SEQ ID NO:92)
Toxin Sequence:
Cys-Leu-Asp-Gly-Gly-Xaa1-Ile-Cys-Gly-Ile-Leu-Phe-Xaa3-Ser-Cys-Cys-Ser-Gly-Xaa4-Cys- (SEQ ID NO:93)
Ile-Val-Leu-Val-Cys-Ala-{circumflex over ( )}
Name: Marm7
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GGTCGACATCATCATCATCGATCCATCTGTCCATCCATCCATCCATTCATTCGCTGCC (SEQ ID NO:94)
AGACTGTAATAAATATTCGAGTCTCTCTTTCTGTTTGTATCTGACAGATTGAACAAG
AGGTGCCTTGAGTTTGGTGAAGTTTGTAATTTTTTTTTCCCAACCTGCTGCGGCTATT
GCGTTCTTCTTGTCTGCCTATAAAACTACCGTGATGTCTTCTACTCCCCTCTAGTAGT
AGTAGGCGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATA
GCTCTTCTATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGA
CTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGC
CAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCA
GCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG
GTGGTTACGCGCAGCGTGACCGCTACACTTGCAGCGCCCTAGCGCCCGCTCCTTTCG
CTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAA
Translation:
LNKRCLEFGEVCNFFFPTCCGYCVLLVCL (SEQ ID NO:95)
Toxin Sequence:
Cys-Leu-Xaa1-Phe-Gly-Xaa1-Val-Cys-Asn-Phe-Phe-Phe-Xaa3-Thr-Cys-Cys-Gly-Xaa5-Cys- (SEQ ID NO:96)
Val-Leu-Leu-Val-Cys-Leu-{circumflex over ( )}
Name: Marm12
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GAAAGCTGGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATC (SEQ ID NO:97)
ATCATCGATCCATCTGTCCATCCATCCATTCATTCATTCGCTGCCAGACTGTAATAA
ATATTCGAGTTTCTCCTTCTGTTTGTATCTGACAGGTTGAACAAGAGGTGCCAAGAG
TTCGGTGAAGTTTGTAATTTTTTTTTCCCAGACTGCTGCGGCTATTGCGTTCTTTTAC
TCTGCATATAAAACTACCGTGATGTCTTCTCTTCCCATCTAGTAGTAGTAGTAGTAG
TAGGCGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGC
TCTTCTATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACCGTCGTGAC
TGGGAAAACCCTGGCGTTCCCAACTTAATTCGCCTTGCAGCACAT
Translation:
LNKRCQEFGEVCNFFFPDCCGYCVLLLCI (SEQ ID NO:98)
Toxin Sequence:
Cys-Gln-Xaa1-Phe-Gly-Xaa1-Val-Cys-Asn-Phe-Phe-Phe-Xaa3-Asp-Cys-Cys-Gly-Xaa5-Cys- (SEQ ID NO:99)
Val-Leu-Leu-Leu-Cys-Ile-{circumflex over ( )}
Name: Omaria7
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
TTTTGAAGCNGGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCA (SEQ ID NO:100)
TCATCATCGATCCATCTGTCCATCCATCCATTCATTCATTCGCTACCAGACTGTAATA
AATATTCGGGTCTCTCTTTCTGTTTGTATCTGACAGATTGGACAAGAGGTGCATTCC
ACATTTTGACCCTTGTGACCCGATACGCCACACCTGCTGCTTTGGCCTGTGCCTACT
AATAGCCTGCATCTAAAACTGCCGTGATGTCTTCTCCTCCCCTCTAGTAGTAGTAGG
CGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTC
TATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGA
AAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTG
GCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGA
ATGGCGAATGGGACGCGCCCTGTAGCGGCGCT
Translation:
LDKRCIPHFDPCDPIRHTCCFGLCLLIACI (SEQ ID NO:101)
Toxin Sequence:
Cys-Ile-Xaa3-His-Phe-Asp-Xaa3-Cys-Asp-Xaa3-Ile-Arg-His-Thr-Cys-Cys-Phe-Gly-Leu-Cys- (SEQ ID NO:102)
Leu-Leu-Ile-Ala-Cys-Ile-{circumflex over ( )}
Name: Omaria11
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
GGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATCATCGATCC (SEQ ID NO:103)
ATCTGTCCATCCATCCATTCTTTCATTTGCTGCCAGACTGTAATAAATATTCGAGTCT
CTCTTTCTGTTTGTATCTGACAGATTGAACAAGAGGTGCCTTGAGTTTGGTGAAGTT
TGTAATTTTTTTTTCCCAACCTGCTGCGGCTATTGCGTTCTTCTTGTCTGCCTATAAA
ACTACCGTGATGTCTTCTCTTCCCCTCTAGTAGTAGTAGGCGGCCGCTCTAGAGGAT
CCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTATAGTGTCACCTAAAT
TCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCC
AACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGG
CCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACGCG
CCCTGTAGCGGCGCATTAAG
Translation:
LNKRCLEFGEVCNFFFPTCCGYCVLLVCL (SEQ ID NO:104)
Toxin Sequence:
Cys-Leu-Xaa1-Phe-Gly-Xaa1-Val-Cys-Asn-Phe-Phe-Phe-Xaa3-Thr-Cys-Cys-Gly-Xaa5-Cys- (SEQ ID NO:105)
Val-Leu-Leu-Val-Cys-Leu-{circumflex over ( )}
Name: O6.5
Species: obscurus
Isolated: No
Cloned: Yes
DNA Sequence:
cgatccatctgtccatccatccattcgttcgttcgctgccaaactgtaataaataaccgagtctctctgtttgtatctgacagATC (SEQ ID NO:106)
GAAAAAGCAATGCCGTCAAAATGGTGAAGTGTGTGATGCGAATTTGGCACACTGCTGCAGT
GGCCCGTGTTTTCTCTTCTGTCTAAACCAGCCGTGATGTCTTCTACTCCCCTC
Translation:
VSDRSKKQCRQNGEVCDANLAHCCSGPCFLFCLNQP (SEQ ID NO:107)
Toxin Sequence:
Ser-Lys-Lys-Gln-Cys-Arg-Gln-Asn-Gly-Xaa1-Val-Cys-Asp-Ala-Asn-Leu-Ala-His-Cys-Cys-Ser- (SEQ ID NO:108)
Gly-Xaa3-Cys-Phe-Leu-Phe-Cys-Leu-Asn-Gln-Xaa3-{circumflex over ( )}
Name: Af6.8
Species: ammiralis
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCATTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:109)
GCCACGGCTGATGACTCCGGAAATGGATTGGAAAATCTTTTTTCGAAGGCACATCA
CGAAATGAAGAACCCCAAAGCCTCTAAATTGAACAAGAGGTGCACTCAAAGCGGTG
AACTTTGTGATGTGATAGACCCAGACTGCTGCAATAATTTTTGCATTATATTTTTCTG
CATATAAAACTGCCGTGATGTCTTCTACTCCCCTC
Translation:
MKLTCVMIIAVLFLTAWTFATADDSGNGLENLFSKAHHEMKNPKASKLNKRCTQSGEL (SEQ ID NO:110)
CDVIDPDCCNNFCIIFFCI
Toxin Sequence:
Cys-Thr-Gln-Ser-Gly-Xaa1-Leu-Cys-Asp-Val-Ile-Asp-Xaa3-Asp-Cys-Cys-Asn-Asn-Phe-Cys- (SEQ ID NO:111)
Ile-Ile-Phe-Phe-Cys-Ile-{circumflex over ( )}
Name: KK-2A
Species: textile
Isolated: No
Cloned: Yes
DNA Sequence:
GGCATTACCTAAAACATCACCAAAATGAAACTGACGTGCATGATGATCGTTGCTGT (SEQ ID NO:112)
GCTGTTCTTGACCGCCTGGACATTCGCCACGGCTGATGACTCCGGAAATGGATTGGA
GAAACTTTTTTCGAATGCACATCACGAAATGAAGAACCCCGAAGCCTCTAATTTGA
ACAAGAGGTGCGCTCCTTTTCTTCACCTTTGTACCTTTTTCTTCCCAAACTGCTGCAA
CGGCTATTGCGTTCAATTTATCTGCCTATAAAACTACTGTGATGTCTTCTATTCCCCT
C
Translation:
MKLTCMMIVAVLFLTAWTFATADDSGNGLEKLFSNAHHEMKNPEASNLNKRCAPFLHL (SEQ ID NO:113)
CTFFFPNCCNGYCVQFICL
Toxin Sequence:
Cys-Ala-Xaa3-Phe-Leu-His-Leu-Cys-Thr-Phe-Phe-Phe-Xaa3-Asn-Cys-Cys-Asn-Gly-Xaa5-Cys- (SEQ ID NO:114)
Val-Gln-Phe-Ile-Cys-Leu-{circumflex over ( )}
Name: KKM1
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCTAGCACAGTGAATTTGGCTTCACAGTTTTCCACTGTCGTCTTTGGCATCATC (SEQ ID NO:115)
CAAAACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTG
ACCGCCTGGACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTT
TCGAAGGCACATCACGAAATGAAGAACCCCAAAGACTCTAAATTGAACAAGAGGT
GCCTTGACGCTGGTGAAATGTGTGATCTTTTTAATTCAAAATGCTGCAGTGGGTGGT
GCATTATTCTCTTCTGCGCATAAAACTACCGTGATGTCTTCTACTCCCCTCTGTGCTA
CCTGGCTTGATCTTTGATTGGCGCGTGCCCTTCACTGGTTATGAACCCCCCTGATCC
GACTCTCTGGCGGCCTCGGGGGTTCAACATCCAAATAAAGCCGACACGATACTGAC
GTAGAAAAAAAAAAAAAAAAAAAAAAAAA
Translation:
MKLTCMMIVAVLFLTAWTFATADDPRNGLENLFSKAHHEMKNPKDSKLNKRCLDAGE (SEQ ID NO:116)
MCDLFNSKCCSGWCIILFCA
Toxin Sequence:
Cys-Leu-Asp-Ala-Gly-Xaa1-Met-Cys-Asp-Leu-Phe-Asn-Ser-Lys-Cys-Cys-Ser-Gly-Xaa4-Cys- (SEQ ID NO:117)
Ile-Ile-Leu-Phe-Cys-Ala-{circumflex over ( )}
Name: KKM4
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GCCGAAAACATCACCAAGATGAAACTGACGAGCATGATGATCGTTGCTGTGCTGTT (SEQ ID NO:118)
CTTGACCGCCTGGACATTCGTCACGGCTGACGACTCCGGAAATGGATTGGAGAATC
TTTTTTCGAAGGCACATCACGAGATGAAGAACCCCAAAGACTCTAAATTGAACAAG
AGGTGCCTTGACGGTGGTGAAATTTGTGGTATTTTGTTTCCAAGCTGCTGCAGTGGG
TGGTGCATTGTTCTCGTCTGCGCATGAAACTACCGTGATGTCTTCTACTCCCCTCTGT
GCTACCTGGCTTGATCTTTGATTGGCGCGTGCCCTTCACTGGTTATGAACCCCCCTG
ATCCGACTCTCTGGCGGCCTCGGGGGTTCAACATCCAAATAAAGCGACACGACAAT
GACAAAAAAAAAAAAAAAAAAAAAAAAAAAA
Translation:
MKLTSMMIVAVLFLTAWTFVTADDSGNGLENLFSKAHHEMKNPKDSKLNKRCLDGGEI (SEQ ID NO:119)
CGILFPSCCSGWCIVLVCA
Toxin Sequence:
Cys-Leu-Asp-Gly-Gly-Xaa1-Ile-Cys-Gly-Ile-Leu-Phe-Xaa3-Ser-Cys-Cys-Ser-Gly-Xaa4-Cys- (SEQ ID NO:120)
Ile-Val-Leu-Val-Cys-Ala-{circumflex over ( )}
Name: KKM5
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GCTAGCACAGTGAATTTGGCTTCACAGTTTTCCACTGTCGTCTTTGGCATCATCCAA (SEQ ID NO:121)
AACATCACCAAGATGAAACTGACGTGCATGATGATCGAAGCAGAGCTGTTCTTGAC
CGCCTGGACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTTTC
GAAGGCACATCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGC
CCTAACACTGGTGAATTATGTGATGTGGTTGAACAAAACTGCTGCTATACCTATTGC
TTTATTGTAGTCTGCCCTATATAACTACCGTGATGTCTTCTACTCCCCTCTGTGCTGC
CTGGCTTGATCTTTGATTGGCGCGTGCCCTTCACTGGTTATGAACCCCCCTGATCCG
ACTCTCTTGCGGCCTCAGGGGTTCAACATCCAAATAAAGCGACACGAAAATGAAAA
AAAAAAAAAAAAAAAAA
Translation:
MKLTCMMIEAELFLTAWTFATADDPRNGLENLFSKAHHEMKNPEASKLNKRCPNTGEL (SEQ ID NO:122)
CDVVEQNCCYTYCFIVVCPI
Toxin Sequence:
Cys-Xaa3-Asn-Thr-Gly-Xaa1-Leu-Cys-Asp-Val-Val-Xaa1-Gln-Asn-Cys-Cys-Xaa5-Thr-Xaa5- (SEQ ID NO:123)
Cys-Phe-Ile-Val-Val-Cys-Xaa3-Ile-{circumflex over ( )}
Name: KKM6
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
TTGCACGGTGAATTTCGCTTATATTTTTCTACTGTCGTCTTTGGCATCATCCAAAACA (SEQ ID NO:124)
TCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCT
GGACATTCGTCACGGCTGTGCCTCACTCCAGCGATGTATTGGAGAATCTTTATCTGA
AGGCACTTCACGAAACGGAAAACCACGAAGCCTCTAAATTGAACGTGAGAGACGA
CGAGTGCGAACCTCCTGGAGATTTTTGTGGCTTTTTTAAAATTGGGCCGCCTTGCTG
CAGTGGCTGGTGCTTCCTCTGGTGCGCCTAAAACTGCCGTGATGTCTTCTATTCCCCT
CTGTGCTACCTGGCTTGATCTTTGATTGGCGCGTGCCCTTCAGTGGTTATGAACCCCC
CTGATCCGACTCTCTGGGGGCCTCGGGGGTTCAACATCCAAATAAAGCTGACAACA
CAATAAAAAAAAAA
Translation:
MKLTCMMIVAVLFLTAWTFVTAVPHSSDVLENLYLKALHETENHEASKLNVRDDECEP (SEQ ID NO:125)
PGDFCGFFKIGPPCCSGWCFLWCA
Toxin Sequence:
Asp-Asp-Xaa1-Cys-Xaa1-Xaa3-Xaa3-Gly-Asp-Phe-Cys-Gly-Phe-Phe-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:126)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Leu-Xaa4-Cys-Ala-{circumflex over ( )}
Name: C. striatus S2
Species: striatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:127)
GTCACGGCTGTGCCTCACTCCAGCGATGCATTGGAGAATCTTTATCTGAAGGCACTT
CACGAAACGGAAAACCACGAAGCCTCTAAATTGAACGTGAGAGACGACGAGTGCG
AACCTCCTGGAGATTTTTGTGGCTTTTTTAAAATTGGGCCGCCTTGCTGCAGTGGCT
GGTGCTTCCTCTGGTGCGCATAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFVTAVPHSSDALENLYLKALHETENHEASKLNVRDDECEP (SEQ ID NO:128)
PGDFCGFFKIGPPCCSGWCFLWCA
Toxin Sequence:
Asp-Asp-Xaa1-Cys-Xaa1-Xaa3-Xaa3-Gly-Asp-Phe-Cys-Gly-Phe-Phe-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:129)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Leu-Xaa4-Cys-Ala-{circumflex over ( )}
Name: Om6.5
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:130)
GTCACGGCTGTGCCTCACTCCAGCAATGCATTGGAAAATCTTTATCTGAAGGCACGT
CACGAAATGGAAAACCCCGAAGCCTCTAAATTGAACACGAGAGACGACGATTGCG
AACCTCCTGGAAATTTTTGTGGCATGATAAAAATTGGGCCGCCTTGCTGCAGTGGCT
GGTGCTTTTTCGCCTGCGCCTAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFVTAVPHSSNALENLYLKARHEMENPEASKLNTRDDDCEP (SEQ ID NO:131)
PGNFCGMIKIGPPCCSGWCFFACA
Toxin Sequence:
Asp-Asp-Asp-Cys-Xaa1-Xaa3-Xaa3-Gly-Asn-Phe-Cys-Gly-Met-Ile-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:132)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Phe-Ala-Cys-Ala-{circumflex over ( )}
Name: Au6.3
Species: aulicus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATAGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:133)
GTCACGGCTGTGCCTCACTCCAGCAATGCATTGGAGAATCTTTATCTGAAGGCACGT
CACGAAATGGAAAACCCCGAAGCCTCTAAATTGAACACGAGAGACTACGATTGCGA
ACCTCCTGGAAATTTTTGTGGCATGATAAAAATTGGGCCGCCTTGCTGCAGTGGCTG
GTGCTTTTTCGCCTGCGCCTAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCLMTVAVLFLTAWTFVTAVPHSSNALENLYLKARHEMENPEASKLNTRDYDCEP (SEQ ID NO:134)
PGNFCGMIKIGPPCCSGWCFFACA
Toxin Sequence:
Asp-Xaa5-Asp-Cys-Xaa1-Xaa3-Xaa3-Gly-Asn-Phe-Cys-Gly-Met-Ile-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:135)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Phe-Ala-Cys-Ala-{circumflex over ( )}
Name: Marm9
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GGTCGACATCATCATCATCATCGATCCATCTGTCCATCCATCTATTCATTCATTCGTG (SEQ ID NO:136)
GCCAAACTGTAATAAATAATGCAAGTCTCTCTTTCTGTTTGTATCTGACAGATTGAA
CACGAGAGACGACGATTGCGAACCTCCTGGAAATTTTTGTGGCATGATAAAAATTG
GGCCGCCTTGCTGCAGTGGCTGGTGCTTTTTCGCCTGCGCCTAAAACTGCCGTGATG
TCTTCTCTTCCCCTCTAGTAGTAGTAGGCGGCCGCTCTAGAGGATCCAAGCTTACGT
ACGCGTGCATGCGACGTCATAGCTCTTCTATAGTGTCACCTAAATTCAATTCACTGG
CCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCC
TTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGAT
CGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGG
CGCATTAAGCGCGGCGGGTGTGGTGGTTACGCCGCAGCCGTGACCCGCTACACTTG
CCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCTTCCTTTCTCGCCACGTTCGCC
GGCTTTTCCCGTCAAGCTCTAAATCGGGGGCTCCTTTAGGGTCCGATTTAAGTGCTT
TAC
Translation:
LNTRDDDCEPPGNFCGMIKIGPPCCSGWCFFACA (SEQ ID NO:137)
Toxin Sequence:
Asp-Asp-Asp-Cys-Xaa1-Xaa3-Xaa3-Gly-Asn-Phe-Cys-Gly-Met-Ile-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:138)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Phe-Ala-Cys-Ala-{circumflex over ( )}
Name: Rg6.4
Species: regius
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAACCAGAGAGACTGCCTTAGTAAAAACGCTTTCTGTGCCTGGCCGATACTTGGA (SEQ ID NO:139)
CCACTGTGCTGCAGTGGCTGGTGCTTATACGTCTGCATGTAAAACTGCCGTGATGTC
TTCTATCCCCTC
Translation:
LNQRDCLSKNAFCAWPILGPLCCSGWCLYVCM (SEQ ID NO:140)
Toxin Sequence:
Asp-Cys-Leu-Ser-Lys-Asn-Ala-Phe-Cys-Ala-Xaa4-Xaa3-Ile-Leu-Gly-Xaa3-Leu-Cys-Cys-Ser- (SEQ ID NO:141)
Gly-Xaa4-Cys-Leu-Xaa5-Val-Cys-Met-{circumflex over ( )}
Name: R6.5
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATTGAACAAGAAAGGTGATGACTGCCTTGCTGTTAAAAAAAATTGTGGCTTTCCAA (SEQ ID NO:142)
AACTTGGAGGGCCATGCTGCAGTGGCTTGTGCTTTTTCGTCTGCGCCTAAAACTGCC
GTGATGTCTTCTCCTCCCCT
Translation:
LNKKGDDCLAVKKNCGFPKLGGPCCSGLCFFVCA (SEQ ID NO:143)
Toxin Sequence:
Gly-Asp-Asp-Cys-Leu-Ala-Val-Lys-Lys-Asn-Cys-Gly-Phe-Xaa3-Lys-Leu-Gly-Gly-Xaa3-Cys- (SEQ ID NO:144)
Cys-Ser-Gly-Leu-Cys-Phe-Phe-Val-Cys-Ala-{circumflex over ( )}
Name: Rg6.2
Species: regius
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAATCAGAGCGACTGCCTTCCTAGAGACACATTCTGTGCCTTGCCGCAACTTGGA (SEQ ID NO:145)
CTACTGTGCTGCAGTGGCCGGTGCTTACTCTTCTGCGTGTAAAACTGCCGTGATGTC
TTCTCCTCCCCTC
Translation:
LNQSDCLPRDTFCALPQLGLLCCSGRCLLFCV (SEQ ID NO:146)
Toxin Sequence:
Asp-Cys-Leu-Xaa3-Arg-Asp-Thr-Phe-Cys-Ala-Leu-Xaa3-Gln-Leu-Gly-Leu-Leu-Cys-Cys-Ser- (SEQ ID NO:147)
Gly-Arg-Cys-Leu-Leu-Phe-Cys-Val-{circumflex over ( )}
Name: A6.5
Species: aurisiacus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGACCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:148)
GTCACGGCTGATGACTCCAGAAATGGACTGAAGAATCTTTTTCCGAAGGCACGTCA
TGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGAGATGGGTGCTCTAATG
CTGGTGCATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGATTTGCATTGTTT
GGTGCACATGAGTCGTATTCTGCTGGTACATTTTGTGGCTTCAACGGAGGACTCTGC
TGCAGCAACCTTTGCTTATTTTTCGTGTGCTTAACATATTCGTGATGTCTTCTACTCC
CATC
Translation:
MKLTCVMTVAVLFLTAWTFVTADDSRNGLKNLFPKARHEMKNPEASKLNKRDGCSNA (SEQ ID NO:149)
GAFCGIHPGLCCSEICIVWCT
Toxin Sequence:
Asp-Gly-Cys-Ser-Asn-Ala-Gly-Ala-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1-Ile- (SEQ ID NO:150)
Cys-Ile-Val-Xaa4-Cys-Thr-{circumflex over ( )}
Name: δ-PVIA
Species: purpurascens
Isolated: Yes
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACTGCCTGGACATTC (SEQ ID NO:151)
GTCACGGCTGATGACTCCAAAAATGGACTGGAGAATCATTTTTGGAAGGCACGTGA
CGAAATGAAGAACCGCGAAGCCTCTAAATTGGACAAAAAGGAAGCCTGCTATGCGC
CTGGTACTTTTTGTGGCATAAAGCCCGGGCTATGCTGCAGTGAGTTTTGTCTCCCGG
GCGTCTGCTTCGGTGGTTAACTGCCGTGATGTCTTCTACTCCCCTCTGTGCTACCTGG
CTTGATCTTTGATCGGCGTGTGCCCTTCACTGGTTATGAACCCACTGATCTTACCTCT
CTTGAAGGACCTCTGGGGTCCAGCATCCAAATAAGCGACATCCCAATGAAAAAAAA
AAAAAAAAAAAAAA
Translation:
MKLTCVMIVAVLFLTAWTFVTADDSKNGLENHFWKARDEMKNREASKLDKKEACYA (SEQ ID NO:152)
PGTFCGIKPGLCCSEFCLPGVCFGG
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Ala-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:153)
Phe-Cys-Leu-Xaa3-Gly-Val-Cys-Phe-Gly-#
Name: δ-PVIA-OH
Species: purpurascens
Isolated: Yes
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Ala-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:153)
Phe-Cys-Leu-Xaa3-Gly-Val-Cys-Phe-Gly-{circumflex over ( )}
Name: δ-PVIA [F9A]
Species: purpurascens
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Ala-Xaa3-Gly-Thr-Ala-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:154)
Phe-Cys-Leu-Xaa3-Gly-Val-Cys-Phe-Gly-{circumflex over ( )}
Name: δ-PVIA [I12A]
Species: purpurascens
Isolated:
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Ala-Xaa3-Gly-Thr-Phe-Cys-Gly-Ala-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:155)
Xaa1-Phe-Cys-Leu-Xaa3-Gly-Val-Cys-Phe-Gly-{circumflex over ( )}
Name: δ-PVIA [T8A]
Species: purpurascens
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Ala-Xaa3-Gly-Ala-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:156)
Phe-Cys-Leu-Xaa3-Gly-Val-Cys-Phe-Gly-{circumflex over ( )}
Name: M6.3
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCACCTGGACATTC (SEQ ID NO:157)
GTCACGGCTGATGACTCCAGATATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCTGAAGCCTCTAAATTGAACAAGAGAGATGGGTGCTATAATGC
TGGTACATTTTGTGGCATCCGTCCAGGACTCTGCTGCAGCGAGTTTTGCTTTTTATGG
TGCATAACATTTGTTGATTCTGGCTAACAGTGTGCGTTGGTTAGTGTCTTCTCCTCCC
CTC
Translation:
MKLTCVMIVAVLFLTTWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKRDGCYNA (SEQ ID NO:158)
GTFCGIRPGLCCSEFCFLWCITFVDSG
Toxin Sequence:
Asp-Gly-Cys-Xaa5-Asn-Ala-Gly-Thr-Phe-Cys-Gly-Ile-Arg-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:159)
Phe-Cys-Phe-Leu-Xaa4-Cys-Ile-Thr-Phe-Val-Asp-Ser-#
Name: M6.6
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCACCTGGACATTC (SEQ ID NO:160)
GTCACGGCTGATGACTCCAGATATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCTGAAGCCTCTAAATTGAACAAGAGAGATGAATGCTATCCTCC
TGGTACATTTTGTGGCATCAAACCAGGACTTTGCTGCAGCGCGATATGCTTATCGTT
TGTCTGCATATCATTTGATTTTTGATTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTTWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKRDECYPPG (SEQ ID NO:161)
TFCGIKPGLCCSAICLSFVCISFDF
Toxin Sequence:
Asp-Xaa1-Cys-Xaa5-Xaa3-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:162)
Ala-Ile-Cys-Leu-Ser-Phe-Val-Cys-Ile-Ser-Phe-Asp-Phe-{circumflex over ( )}
Name: M6.7
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTACTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:163)
GTCACGGCTGATGACTCCAGATATGGACTGAAGGATCTGTTTCCGAAGGAACGTCA
TGAAATGAAGAACCCCGAAGCCTCTAAATTGAACCAGAGAGAAGCCTGCTATAATG
CTGGTTCATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGTTTTGCATTCTTTG
GTGCATAACATTTGTTGATTCTGGCTAACTGTGTGCGTTGGTTGATGTCTTCTCCTCC
CATC
Translation:
MKLTCVMIVAVLFLTAWTFVTADDSRYGLKDLFPKERHEMKNPEASKLNQREACYNA (SEQ ID NO:164)
GSFCGIHPGLCCSEFCILWCITFVDSG
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Asn-Ala-Gly-Ser-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:165)
Phe-Cys-Ile-Leu-Xaa4-Cys-Ile-Thr-Phe-Val-Asp-Ser-#
Name: M6.8
Species: magus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTACTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:166)
GTCACGGCTGATGACTCCAGATATGGACTGAAGGATCTGTTTCCGAAGGAACGTCA
TGAAATGAAGAACCCCGAAGCCTCTAAATTGAACCAGAGAGAAGCCTGCTATAATG
CTGGTACATTTTGTGGCATCAAACCAGGACTTTGCTGCAGCGCGATATGCTTATCGT
TTGTCTGCATATCATTTGATTTTTGATTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRYGLKDLFPKERHEMKNPEASKLNQREACYNA (SEQ ID NO:167)
GTFCGIKPGLCCSAICLSFVCISFDF
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Asn-Ala-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Ala- (SEQ ID NO:168)
Ile-Cys-Leu-Ser-Phe-Val-Cys-Ile-Ser-Phe-Asp-Phe-
Name: E6.4
Species: ermineus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACTGCCTGGACATTC (SEQ ID NO:169)
GTCACGGCTGATGACTCCAAAAATGGACTGGAGAATCATTTTTGGAAGGCACGTGA
CGAAATGAAGAACCGCGAAGCCTCTAAATTGGACAAAAAGGAAGCCTGCTATCCGC
CTGGTACTTTTTGTGGCATAAAGCCCGGGCTATGCTGCAGTGAGTTGTGTTTACCGG
CCGTCTGCGTCGGTGGTTAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFVTADDSKNGLENHFWKARDEMKNREASKLDKKEACYPP (SEQ ID NO:170)
GTFCGIKPGLCCSELCLPAVCVGG
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Xaa3-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:171)
Xaa1-Leu-Cys-Leu-Xaa3-Ala-Val-Cys-Val-Gly-#
Name: P6.4
Species: purpurascens
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACTGCCTGGACATTC (SEQ ID NO:172)
GTCACGGCTGATGACTCCAAAAATGGACTGGAGAATCATTTTTGGAAGGCACGTGA
CGAAATGAAGAACCGCGAAGCCTCTAAATTGGACAAAAAGGAAGCCTGCTATCCGC
CTGGTACTTTTTGTGGCATAAAGCCCGGGCTATGCTGCAGTGAGTTGTGTTTACCGG
CCGTCTGCGTCGGTGGTTAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSKNGLENHFWKARDEMKNREASKLDKKEACYP (SEQ ID NO:173)
PGTFCGIKPGLCCSELCLPAVCVGG
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Xaa3-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:174)
Xaa1-Leu-Cys-Leu-Xaa3-Ala-Val-Cys-Val-Gly-#
Name: δ-SVIE [D1E]
Species: striatus
Isolated: Yes
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCACTTGGACATTC (SEQ ID NO:175)
GTCACGGCTGATGACTCCAGATATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGAGAAGGGTGCTCTAGTG
GTGGTACATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGTTTTGCTTTCTTTG
GTGCATAACATTTATTGATTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTTWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKREGCSSGG (SEQ ID NO:176)
TFCGIHPGLCCSEFCFLWCITFID
Toxin Sequence:
Xaa1-Gly-Cys-Ser-Ser-Gly-Gly-Thr-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:177)
Phe-Cys-Phe-Leu-Xaa4-Cys-Ile-Thr-Phe-Ile-Asp-{circumflex over ( )}
Name: δ-SVIE
Species: striatus
Isolated: Yes
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCACTTGGACATTC (SEQ ID NO:178)
GTCACGGCTGATGACTCCAGATATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGAGATGGGTGCTCTAGTGG
TGGTACATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGTTTTGCTTTCTTTGG
TGCATAACATTTATTGATTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTTWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKRDGCSSGG (SEQ ID NO:179)
TFCGIHPGLCCSEFCFLWCITFID
Toxin Sequence:
Asp-Gly-Cys-Ser-Ser-Gly-Gly-Thr-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1-Phe- (SEQ ID NO:180)
Cys-Phe-Leu-Xaa4-Cys-Ile-Thr-Phe-Ile-Asp-{circumflex over ( )}
Name: δ-NgVIA
Species: striolatus
Isolated: Yes
Toxin Sequence:
Ser-Lys-Cys-Phe-Ser-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser-Val-Arg- (SEQ ID NO:181)
Cys-Phe-Ser-Leu-Phe-Cys-Ile-Ser-Phe-Xaa1-{circumflex over ( )}
Name: C6.2
Species: catus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:182)
GTCACGGCTGATGACTCCAGAAATGGACTGAAGAATCTTTTTCCGAAGGCACGTCA
TGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGATATGGGTGCTCTAATG
CTGGTGCATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGCTTTGCCTGGTTT
GGTGCACATGAGTGCTATTCTTCTGGTACATTTTGTGGCTTCAACGGAGGACTCTGC
TGCAGCAACCTTTGCTTATTTTCGTGTGCTTAACATTTCGTGATGTCTTCTCTATTCC
CCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRNGLKNLFPKARHEMKNPEASKLNKRYGCSNA (SEQ ID NO:183)
GAFCGIHPGLCCSELCLVWCT
Toxin Sequence:
Xaa5-Gly-Cys-Ser-Asn-Ala-Gly-Ala-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:184)
Leu-Cys-Leu-Val-Xaa4-Cys-Thr-{circumflex over ( )}
Name: C6.3
Species: catus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:185)
GTCACGGCTGATGACTCCAGATATGGACTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGATATGGGTGCTCTAATGC
TGGTGCATTTTGTGGCATCCATCCAGGACTCTGCTGCAGCGAGCTTTGCCTGGGTTG
GTGCACATGAGTGCTATTCTACTGGTACATTTTGTGGCTTCAACGGAGGACTCTGCT
GCAGCAACCTTTGCTTATTTTCGTGTGCTTAACATTTCGTGATGTCTTCTCTATTCCC
CTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKRYGCSNA (SEQ ID NO:186)
GAFCGIHPGLCCSELCLGWCT
Toxin Sequence:
Xaa5-Gly-Cys-Ser-Asn-Ala-Gly-Ala-Phe-Cys-Gly-Ile-His-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:187)
Leu-Cys-Leu-Gly-Xaa4-Cys-Thr-{circumflex over ( )}
Name: Di6.3
Species: distans
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTCTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:188)
GTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTCTCTCCGAAGGCACCTCA
CGAAATGAAGAACCCCGAAGCCTCTAAATCGAACAAGAGATATGAGTGCTATCTAC
TGGTACATTTTTGTGGCATCAACGGAGGACTCTGCTGCAGCAACCTTTGCTTATTTTT
CGTGTGCTTAACATTTTCGTGATGTCTTCTCCTCCCATC
Translation:
MKLTCLMIVAVLFLTAWTFVTADDSRNGLENLSPKAPHEMKNPEASKSNKRYECYLLV (SEQ ID NO:189)
HFCGINGGLCCSNLCLFFVCLTFS
Toxin Sequence:
Xaa5-Xaa1-Cys-Xaa5-Leu-Leu-Val-His-Phe-Cys-Gly-IIe-Asn-Gly-Gly-Leu-Cys-Cys-Ser-Asn- (SEQ ID NO:190)
Leu-Cys-Leu-Phe-Phe-Val-Cys-Leu-Thr-Phe-Ser-{circumflex over ( )}
Name: Rg6.1
Species: regius
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAGCAAGAGAGACTGCCTTCCTGACTACACGATTTGTGCCTTCAATATGGGTCTG (SEQ ID NO:191)
TGCTGCAGCGACAAGTGCATGCTCGTCTGCCTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
LSKRDCLPDYTICAFNMGLCCSDKCMLVCLP (SEQ ID NO:192)
Toxin Sequence:
Asp-Cys-Leu-Xaa3-Asp-Xaa5-Thr-Ile-Cys-Ala-Phe-Asn-Met-Gly-Leu-Cys-Cys-Ser-Asp-Lys- (SEQ ID NO:193)
Cys-Met-Leu-Val-Cys-Leu-Xaa3-{circumflex over ( )}
Name: Rg6.3
Species: regius
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAACAAGAGAATCATCTGCTTTCCTGACTACATGTTTTGTGGCGTCAATGTGTTTC (SEQ ID NO:194)
TGTGCTGCAGTGGCAACTGCCTTCTCATCTGCGTGCCGTGATGTCTTCTACTCCCCTC
Translation:
LNKRIICFPDYMFCGVNVFLCCSGNCLLICVP (SEQ ID NO:195)
Toxin Sequence:
Ile-Ile-Cys-Phe-Xaa3-Asp-Xaa5-Met-Phe-Cys-Gly-Val-Asn-Val-Phe-Leu-Cys-Cys-Ser-Gly- (SEQ ID NO:196)
Asn-Cys-Leu-Leu-Ile-Cys-Val-Xaa3-{circumflex over ( )}
Name: Gm6.2
Species: gloriamaris
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:197)
GTCACGGCTGTGCCTCACTCCAGCAATGCGTTGGAGAATCTTTATCTGAAGGCACAT
CATGAAATGAACAACCCCGAAGACTCTGAATTGAACAAGAGGTGCTATGATGGTGG
GACAGGTTGTGACTCTGGAAACCAATGCTGCAGTGGCTGGTGCATTTTCGCCTGCCT
CTAAAACTGTCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTAVPHSSNALENLYLKAHHEMNNPEDSELNKRCYDGG (SEQ ID NO:198)
TGCDSGNQCCSGWCIFACL
Toxin Sequence:
Cys-Xaa5-Asp-Gly-Gly-Thr-Gly-Cys-Asp-Ser-Gly-Asn-Gln-Cys-Cys-Ser-Gly-Xaa4-Cys-Ile- (SEQ ID NO:199)
Phe-Ala-Cys-Leu-{circumflex over ( )}
Name: Da6.1
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATTATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:200)
GTCACGGCTGTGCCTCACTCCAGCAATGCGTTGGAGAATCTTTATCTGAAGGCACAT
CATGAAATGAACAACCCCGAGGACTCTGAATTGAACAAGAGGTGCTATGATGGTGG
GACAGGTTGTGACTCTGGAAACCAATGCTGCAGTGGCTGGTGCATTTTCGTCTGCCT
CTAAAACTGCCGTGATGTCTTCTCTCCCATC
Translation:
MKLTCIMIVAVLFLTAWTFVTAVPHSSNALENLYLKAHHEMNNPEDSELNKRCYDGGT (SEQ ID NO:201)
GCDSGNQCCSGWCIFVCL
Toxin Sequence:
Cys-Xaa5-Asp-Gly-Gly-Thr-Gly-Cys-Asp-Ser-Gly-Asn-Gln-Cys-Cys-Ser-Gly-Xaa4-Cys-Ile- (SEQ ID NO:202)
Phe-Val-Cys-Leu-{circumflex over ( )}
Name: Pn6.6
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACAGTC (SEQ ID NO:203)
GTCACGGCTGTGCCTCACTCCAACAAGCGGTTGGCGAATCTTTATCTGAAGGCACGT
CACGAAATGAAAAACCCCGAAGCCTCTAATGTGGACAAGAGGTGCTTTGAGAGTTG
GGTAGCTTGTGAGTCTCCAAAACGATGCTGCAGTCACGTGTGCCTTTTCGTCTGCAC
CTGAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTVVTAVPHSNKRLANLYLKARHEMKNPEASNVDKRCFESW (SEQ ID NO:204)
VACESPKRCCSHVCLFVCT
Toxin Sequence:
Cys-Phe-Xaa1-Ser-Xaa4-Val-Ala-Cys-Xaa1-Ser-Xaa3-Lys-Arg-Cys-Cys-Ser-His-Val-Cys-Leu- (SEQ ID NO:205)
Phe-Val-Cys-Thr-{circumflex over ( )}
Name: Di6.5
Species: distans
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTATGTTGATCATCGCTGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ ID NO:206)
TCTACAAATGCGAGTTACGCCAGAAGTAAGCAGAAGCATCGTGTTCTGAGGTCGAC
TGACAAAAACTCCAAGTTGACCCAGCGTTGCAATGAAGCTCAAGAACATTGCACTC
AAAATCCTGACTGCTGCAGTGAGTCTTGCAATAAGTTTGTCGGCAGATGCTTGTCAG
ACTGATCTGATGTCTTCTCCTCCCATC
Translation:
MKLTCMLIIAVLFLTACQLSTNASYARSKQKHRVLRSTDKNSKLTQRCNEAQEHCTQNP (SEQ ID NO:207)
DCCSESCNKFVGRCLSD
Toxin Sequence:
Cys-Asn-Xaa1-Ala-Gln-Xaa1-His-Cys-Thr-Gln-Asn-Xaa3-Asp-Cys-Cys-Ser-Xaa1-Ser-Cys- (SEQ ID NO:208)
Asn-Lys-Phe-Val-Gly-Arg-Cys-Leu-Ser-Asp-{circumflex over ( )}
Name: Af6.10
Species: ammiralis
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:209)
GTCACGGCTGTGCCTGACTCCAGCAATGCGTTGGAGAATCTTTATCTGAAGGCACAT
CATGAAATGAACAACCCCGAAGACTCTGAATTGAACAAGAGGTGCTATGATGGTGG
GACAAGTTGTAACACTGGAAACCAATGCTGCAGTGGCTGGTGCATTTTCCTCTGCCT
CTAAAACTGCCGTGATGTCTTCTCTTCCCCTC
Translation:
MKLTCLMIVAVLFLTAWTFVTAVPDSSNALENLYLKAHHEMNNPEDSELNKRCYDGGT (SEQ ID NO:210)
SCNTGNQCCSGWCIFLCL
Toxin Sequence:
Cys-Xaa5-Asp-Gly-Gly-Thr-Ser-Cys-Asn-Thr-Gly-Asn-Gln-Cys-Cys-Ser-Gly-Xaa4-Cys-Ile- (SEQ ID NO:211)
Phe-Leu-Cys-Leu-{circumflex over ( )}
Name: Tx6.10
Species: textile
Isolated: No
Cloned: Yes
DNA Sequence:
GGCATTACCTAAAACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGT (SEQ ID NO:212)
GCTGTTCTTGACCGCCTGGACATTCGTCACGGCTGCGCCTCACTCCAGCAATGCGTT
GGAGAATCTTTATCTGAAGGCACATCATGAAATGAACAACCCCGAAGCCTCTGAAT
TGAACAAGAGGTGCTATGATAGTGGGACAAGTTGTAACACTGGAAACCAATGCTGC
AGTGGCTGGTGCATTTTCGTCTCTTGCCTCTAAAACTACCGTGATGTCTTCTCCTCCC
CTC
Translation:
MKLTCMMIVAVLFLTAWTFVTAAPHSSNALENLYLKAHHEMNNPEASELNKRCYDSG (SEQ ID NO:213)
TSCNTGNQCCSGWCIFVSCL
Toxin Sequence:
Cys-Xaa5-Asp-Ser-Gly-Thr-Ser-Cys-Asn-Thr-Gly-Asn-Gln-Cys-Cys-Ser-Gly-Xaa4-Cys-Ile- (SEQ ID NO:214)
Phe-Val-Ser-Cys-Leu-{circumflex over ( )}
Name: Gm6.4
Species: gloriamaris
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCCTGACAGCCTGGACGCTA (SEQ ID NO:215)
GTCATGGCTGATGACTCCAACAATGGACTGGCGAATCTTTTTTCGAAATCACGTGAC
GAAATGGAGGACCCCGAAGCTTCTAAATTGGAGAAAAGGGATTGCCAAGCACTATG
GGATTATTGTCCAGTACCGCTCTTGTCATCGGGTGATTGCTGCTATGGCTTAATCTGT
GGCCCTTTCGTCTGCATTGGATGGTGATGTCTTCTACTCCCATC
Translation:
MKLTCMMIVAVLFLTAWTLVMADDSNNGLANLFSKSRDEMEDPEASKLEKRDCQALW (SEQ ID NO:216)
DYCPVPLLSSGDCCYGLICGPFVCIGW
Toxin Sequence:
Asp-Cys-Gln-Ala-Leu-Xaa4-Asp-Xaa5-Cys-Xaa3-Val-Xaa3-Leu-Leu-Ser-Ser-Gly-Asp-Cys- (SEQ ID NO:217)
Cys-Xaa5-Gly-Leu-Ile-Cys-Gly-Xaa3-Phe-Val-Cys-Ile-Gly-Xaa4-{circumflex over ( )}
Name: Om6.2
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:218)
GTCATGGCTGATGACTCCAACAATGGACTGGCAAATCTTTTCTCGAAATCACGTGAC
GAAATGGAGGATACCGATCCTTCTAAATTGGAGAACAGAAAAACTTGCCAAAGAAG
GTGGGATTTTTGTCCAGGATCGCTCGTTGGAGTGATAACTTGCTGCGGTGGCTTAAT
CTGTTTTCTGTTCTTCTGCGTTTGATAGTGATGCTCTTCTCCTCCCCT
Translation:
MKLTCLMIVAVLFLTAWTFVMADDSNNGLANLFSKSRDEMEDTDPSKLENRKTCQRR (SEQ ID NO:219)
WDFCPGSLVGVITCCGGLICFLFFCV
Toxin Sequence:
Lys-Thr-Cys-Gln-Arg-Arg-Xaa4-Asp-Phe-Cys-Xaa3-Gly-Ser-Leu-Val-Gly-Val-Ile-Thr-Cys- (SEQ ID NO:220)
Cys-Gly-Gly-Leu-Ile-Cys-Phe-Leu-Phe-Phe-Cys-Val-{circumflex over ( )}
Name: Da6.3
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCCTGACAGCCTGGACGCTA (SEQ ID NO:221)
GTCATGGCTGATGACTCCAACAATGGACTGGCGAATCTTTTTTCGAAATTACGTGAC
GAAATGGAGGACCCCGAAGGTTCTAAATTGGAGAAAAAGGATTGCCAAGAAAAAT
GGGATTATTGTCCAGTACCGTTCTTGGGATCGAGGTATTGCTGCGATGGCTTTATCT
GTCCATCTTTCTTCTGCGCTTGATAGTGATGTCTTCTCTATTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTLVMADDSNNGLANLFSKLRDEMEDPEGSKLEKKDCQEKW (SEQ ID NO:222)
DYCPVPFLGSRYCCDGFICPSFFCA
Toxin Sequence:
Asp-Cys-Gln-Xaa1-Lys-Xaa4-Asp-Xaa5-Cys-Xaa3-Val-Xaa3-Phe-Leu-Gly-Ser-Arg-Xaa5-Cys- (SEQ ID NO:223)
Cys-Asp-Gly-Phe-Ile-Cys-Xaa4-Ser-Phe-Phe-Cys-Ala-{circumflex over ( )}
Name: Da6.7
Species: dalli
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGTTGTTCCTGACAGCCTGGACGCTA (SEQ ID NO:224)
GTCATGGCTGATGACTCCAACAATGGACTGGCGAATCATTTTTGGAAATCACGTGAC
GAAATGGAGGACCCTGAAGCTTCTAAATTGGAGAAAAGGGATTGCCAAGGCGAATG
GGAGTTTTGTATAGTACCGGTCCTTGGATTTGTGTATTGCTGCCCCTGGCTTATCTGT
GGCCCTTTCGTCTGCGTTGATATCTGATGTCTTCTATCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTLVMADDSNNGLANHFWKSRDEMEDPEASKLEKRDCQGE (SEQ ID NO:225)
WEFCIVPVLGFVYCCPWLICGPFVCVDI
Toxin Sequence:
Asp-Cys-Gln-Gly-Xaa1-Xaa4-Xaa1-Phe-Cys-Ile-Val-Xaa3-Val-Leu-Gly-Phe-Val-Xaa5-Cys- (SEQ ID NO:226)
Cys-Xaa3-Xaa4-Leu-Ile-Cys-Gly-Xaa3-Phe-Val-Cys-Val-Asp-Ile-{circumflex over ( )}
Name: Pn6.5
Species: pennaceus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCATTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:227)
GTCATGGCTGATGACCCCAGAGATGAACCGGAGGCACGTGACGAAATGAACCCCGC
AGCCTCTAAATTGAACGAGAGAGGCTGCCTTGAAGTTGATTATTTTTGCGGCATACC
GTTTGTGAACAACGGGCTATGCTGCAGTGGCAATTGTGTTTTTGTCTGCACACCCCA
AGGGAAGTAAAACTGCTGTGATGTCTTCTCTTCCCATC
Translation:
MKLTCLMIIAVLFLTAWTFVMADDPRDEPEARDEMNPAASKLNERGCLEVDYFCGIPFV (SEQ ID NO:228)
NNGLCCSGNCVFVCTPQGK
Toxin Sequence:
Gly-Cys-Leu-Xaa1-Val-Asp-Xaa5-Phe-Cys-Gly-Ile-Xaa3-Phe-Val-Asn-Asn-Gly-Leu-Cys-Cys- (SEQ ID NO:229)
Ser-Gly-Asn-Cys-Val-Phe-Val-Cys-Thr-Xaa3-Gln-#
Name: Marm6
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GGTCGACATCATCATCATCGATCCATCTGTCCATCCATCTGTCCATCCATCCATTCAT (SEQ ID NO:230)
TCATTCACTGCCAAACTGTCATAAATATTTGAGTCTCTCTTTCTGTTTTTATCTGACA
GATTGAACGAGAGAGACTGCCTTAATGTTGATTATTTTTGCGGCATACCGTTTGTGA
ACAACGGGCTATGCTGCAGTGGCAATTGTGTTTTTGTCTGCACACCCCAAGGGAAGT
AAAACTGCCGTGATGTCTTCTCTTCCCCTCTAGTAGTAGTAGGCGGCCGCTCTAGAG
GATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTATAGTGTCACCTA
AATTCAATTCACTGGCCGTCCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTT
ACCCAACTTAATCGCCTTGCAGCACAT
Translation:
NERDCLNVDYFCGIPFVNNGLCCSGNCVFVCTPQGK (SEQ ID NO:231)
Toxin Sequence:
Cys-Leu-Asn-Val-Asp-Xaa5-Phe-Cys-Gly-Ile-Xaa3-Phe-Val-Asn-Asn-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:232)
Gly-Asn-Cys-Val-Phe-Val-Cys-Thr-Xaa3-Gln-#
Name: Marm15
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
TCGACATCATCATCATCGATCCATCTGTCCATCCATCCATTCATTCATTCGCTGCCAA (SEQ ID NO:233)
ACTGTCATAAATATTTGAGTCTCTCTTTCTGTTTTTATCTGACAGATTGGACAAGAGA
GAGTGCCTGGAAGCTGATTATTATTGCGTCTTACCGTTTGTGGGCAACGGGATGTGC
TGCAGTGGCATTTGTGTTTTTGTCTGCATAGCCC
Translation:
LDKRECLEADYYCVLPFVGNGMCCSGICVFVCIAQRFKTV (SEQ ID NO:234)
Toxin Sequence:
Xaa1-Cys-Leu-Xaa1-Ala-Asp-Xaa5-Xaa5-Cys-Val-Leu-Xaa3-Phe-Val-Gly-Asn-Gly-Met-Cys- (SEQ ID NO:235)
Cys-Ser-Gly-Ile-Cys-Val-Phe-Val-Cys-Ile-Ala-Gln-Arg-Phe-Lys-Thr-Val-{circumflex over ( )}
Name: Marm10
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GTACCGGTCCGGAATTCCCGGGTCGACATCATCATCATCGATCCATCTGTCCATCCA (SEQ ID NO:236)
TCCATCCATTCATTCATTCGCTGCCAAACTGTCATAAACATTTGAGTCTCTCTTTCTG
TTTTTATCTGACAGATTGAACGAGAGAGACTGCCTTGAACCTGATTATGTTTGCGGC
ATACCGTTTGTGTTCAACGGGCTATGCTGCAGTGGAATTTGTGTTTTTATCTGCATAG
CCCAAAAGTATTAAAACGCCGTGATGTCTTCTATTCCCATCTAGTAGTAGTAGGCGG
CCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTAT
AGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAA
CCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCG
TAATAGCCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAAT
GGCGAATGGGG
Translation:
LNERDCLEPDYVCGIPFVFNGLCCSGICVFICIAQKY (SEQ ID NO:237)
Toxin Sequence:
Asp-Cys-Leu-Xaa1-Xaa3-Asp-Xaa5-Val-Cys-Gly-Ile-Xaa3-Phe-Val-Phe-Asn-Gly-Leu-Cys- (SEQ ID NO:238)
Cys-Ser-Gly-Ile-Cys-Val-Phe-Ile-Cys-Ile-Ala-Gln-Lys-Xaa5-{circumflex over ( )}
Name: Marm14
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
GGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATCATCATCGA (SEQ ID NO:239)
TCCATCTGTCCATCCATCTATTCATTCATTCGCTGTCAAACTGTAATACATATTAGAA
TCTCTCTTTCTGTTTGTATCTGACAGATTGGAGAAAAGGGCGTGCAGCAAAAAATGG
GAATATTGTATAGTACCGATCCTTGGATTCGTATATTGCTGCCCTGGCTTAATCTGTG
GTCCTTTCGTCTGCGTTTGATAGTGATGTCTTCTCCTCCCATCTAGTAGTAGTAGGCG
GCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTA
TAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAA
ACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGC
GTAATAAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAA
TGGCGAAATGGGACGCGCCCTG
Translation:
LEKRACSKKWEYCIVPILGFVYCCPGLICGPFVCV (SEQ ID NO:240)
Toxin Sequence:
Ala-Cys-Ser-Lys-Lys-Xaa4-Xaa1-Xaa5-Cys-Ile-Val-Xaa3-Ile-Leu-Gly-Phe-Val-Xaa5-Cys-Cys- (SEQ ID NO:241)
Xaa3-Gly-Leu-Ile-Cys-Gly-Xaa3-Phe-Val-Cys-Val-{circumflex over ( )}
Name: Omaria14
Species: omaria
Isolated: No
Cloned: Yes
DNA Sequence:
AAAGCCGGTACGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATCA (SEQ ID NO:242)
TCATCGATCCATCTGTCCATCCATCCATTCATTCATTCACTGCCAAACTGTCATAAAT
ATTTGAGTCTCTCTTTCTGTTTTTATCTGACAGATTGAACGAGAGAGACTGCCTTAAT
GTTGATTATTTTTGTGGCATACCGTTTGTGAACAACGGGCTATGCTGCAGTGGCAAT
TGTGTTTTTTGTCTGCACACCCCAAGGGAAGTAAAACTGCCGTGATGTCTTCTCTTCC
CCTCTAGTAGTAGTAGGCGGCCGCTCTAGAGGATCCAAGCTTACGTACGCGTGCAT
GCGACGTCATAGCTCTTCTATAGTGTCACCTAAATTCAATTCACTGGCCGTCGTTTTA
CAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACAT
CCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCA
ACAGTTGCGCAGCCTGAATGGCGAATGGGACGCGCCCT
Translation:
LNERDCLNVDYFCGIPFVNNGLCCSGNCVFCLHTPREVKLP (SEQ ID NO:243)
Toxin Sequence:
Asp-Cys-Leu-Asn-Val-Asp-Xaa5-Phe-Cys-Gly-Ile-Xaa3-Phe-Val-Asn-Asn-Gly-Leu-Cys-Cys- (SEQ ID NO:244)
Ser-Gly-Asn-Cys-Val-Phe-Cys-Leu-His-Thr-Xaa3-Arg-Xaa1-
Name: O6.4
Species: obscurus
Isolated: No
Cloned: Yes
DNA Sequence:
cgatccatctgtccatccatccattcattcattcattgccaaactgtaacaaatattcaagtctctctttctgtttgtgtctgaca (SEQ ID NO:245)
gATCGAAACGGTGCCTTGTTTACGGTACACCTTGTGACTGGCTGACCATTGCGGGTATGGAGTGC
TGCAGTAAAAAGTGCTTTATGATGTGCTGGTAAAACTGCCGTGATGTCTTCTACTCC
CCTC
Translation:
RSKRCLVYGTPCDWLTIAGMECCSKKCFMMCW (SEQ ID NO:246)
Toxin Sequence:
Cys-Leu-Val-Xaa5-Gly-Thr-Xaa3-Cys-Asp-Xaa4-Leu-Thr-Ile-Ala-Gly-Met-Xaa1-Cys-Cys-Ser- (SEQ ID NO:247)
Lys-Lys-Cys-Phe-Met-Met-Cys-Xaa4-{circumflex over ( )}
Name: R6.4
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATTGAACCAGAGAGACTGCCATGAAGTTGGTGAATTTTGTGGCTTACCGTTAATAAA (SEQ ID NO:248)
GAACGGGCTATGCTGCAGTCAGATTTGTTTAGGTGTCTGCGCAAAAGTGTTTTAAAA
CTGCCGTGATGTCTTCTACTCCCAT
Translation:
LNQRDCHEVGEFCGLPLIKNGLCCSQICLGVCAKVF (SEQ ID NO:249)
Toxin Sequence:
Asp-Cys-His-Xaa1-Val-Gly-Xaa1-Phe-Cys-Gly-Leu-Xaa3-Leu-Ile-Lys-Asn-Gly-Leu-Cys-Cys- (SEQ ID NO:250)
Ser-Gln-Ile-Cys-Leu-Gly-Val-Cys-Ala-Lys-Val-Phe-{circumflex over ( )}
Name: R6.6
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATTAGACAAGAAAGAGTGCACTGCCAATGGTGAATTTTGTGGCATATCGGTCTTTGG (SEQ ID NO:251)
AAGCTACCTATGCTGCAGTGGCCGGTGTGTATTCGTCTGCATCTAGTTGAACTGCCG
TGATGTCTTCTACTCCCCT
Translation:
LDKKECTANGEFCGISVFGSYLCCSGRCVFVCI (SEQ ID NO:252)
Toxin Sequence:
Xaa1-Cys-Thr-Ala-Asn-Gly-Xaa1-Phe-Cys-Gly-Ile-Ser-Val-Phe-Gly-Ser-Xaa5-Leu-Cys-Cys- (SEQ ID NO:253)
Ser-Gly-Arg-Cys-Val-Phe-Val-Cys-Ile-{circumflex over ( )}
Name: R6.7
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATTGGACAAGAAAGAGTGCACTACCAATGGTGAATTTTGTGGCATATCGGTCTTTGC (SEQ ID NO:254)
AAGCTTCCTATGCTGCAGTGGCCTGTGTGTATTCGTCTGCATCTAGCTGAACTGCCG
TGATGTCTTCTCTTCCCCT
Translation:
LDKKECTTNGEFCGISVFASFLCCSGLCVFVCI (SEQ ID NO:255)
Toxin Sequence:
Xaa1-Cys-Thr-Thr-Asn-Gly-Xaa1-Phe-Cys-Gly-Ile-Ser-Val-Phe-Ala-Ser-Phe-Leu-Cys-Cys-Ser- (SEQ ID NO:256)
Gly-Leu-Cys-Val-Phe-Val-Cys-Ile-{circumflex over ( )}
Name: R6.8
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATTGGACAAGAGAAAATGCTTTCCCAAAAATCATTTTTGTGGCTTTGTGGTGATGCT (SEQ ID NO:257)
GAACTACCTATGCTGCAGTGGCCGGTGTATATTCGTCTGCGTCTAGTTGAACTGCCG
TGATGTCTTCTACTCCCAT
Translation:
LDKRKCFPKNHFCGFVVMLNYLCCSGRCIFVCV (SEQ ID NO:258)
Toxin Sequence:
Lys-Cys-Phe-Xaa3-Lys-Asn-His-Phe-Cys-Gly-Phe-Val-Val-Met-Leu-Asn-Xaa5-Leu-Cys-Cys- (SEQ ID NO:259)
Ser-Gly-Arg-Cys-Ile-Phe-Val-Cys-Val-{circumflex over ( )}
Name: Rg6.5
Species: regius
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAACAAGAGAAGCTGCCTTCCTCTAGACTGGTTTTGTGGCTTCAATATAATTGGA (SEQ ID NO:260)
GCGTTTCTGTGCTGTAGTGGCTACTGCCTTGTCGTCTGCATGTAAAACTGCCGTGAT
GTCTTCTCCTCCCCTC
Translation:
LNKRSCLPLDWFCGFNIIGAFLCCSGYCLVVCM (SEQ ID NO:261)
Toxin Sequence:
Ser-Cys-Leu-Xaa3-Leu-Asp-Xaa4-Phe-Cys-Gly-Phe-Asn-Ile-Ile-Gly-Ala-Phe-Leu-Cys-Cys-Ser- (SEQ ID NO:262)
Gly-Xaa5-Cys-Leu-Val-Val-Cys-Met-{circumflex over ( )}
Name: De6.2
Species: delessertii
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTCTGCTGATCGTTGCTGTGCTGGTCTTGGCAGCCTGTCAGTTC (SEQ ID NO:263)
ATCGTAGCTGGCGACTCGAGTGATGGCCAGGAGAATCCTGCTCTGAGGTCACCTAG
CGATTCCTCTGGGAAAATGTCATCAATGAAGCGCTTCCAGACACGGCTGATGGTGG
GGCAATCTGCATCGAAAAGACCAAGCAAGAGGGACTGCATCCCCGGCGGCGAAAA
TTGTGATGTATTCCGACCATACCGGTGCTGCAGTGGATATTGCATACTACTCCTTTG
CGCATGATAAAGCTGCCTTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCLLIVAVLVLAACQFIVAGDSSDGQENPALRSPSDSSGKMSSMKRFQTRLMVGQS (SEQ ID NO:264)
ASKRPSKRDCIPGGENCDVFRPYRCCSGYCILLLCA
Toxin Sequence:
Asp-Cys-Ile-Xaa3-Gly-Gly-Xaa1-Asn-Cys-Asp-Val-Phe-Arg-Xaa3-Xaa5-Arg-Cys-Cys-Ser-Gly- (SEQ ID NO:265)
Xaa5-Cys-Ile-Leu-Leu-Leu-Cys-Ala-{circumflex over ( )}
Name: Striat21
Species: striatus
Isolated: No
Cloned: Yes
DNA Sequence:
GCTGGTTCGCCTGCAGGTACCGGTCCGGAATTCCCGGGTCGACATCATCATCATCGA (SEQ ID NO:266)
TCCATCTGTCCATCCATCTATTCATTCATTCATTCGCTGCCAAACTGTATTAAATATT
CAAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGATGGTGCATTCCTAGTGGTGA
ACTTTGTTTCCGCTCGGATCACATAGGATGCTGCAGTGGCAAGTGCGCATTCGTCTG
CTTGTAAAACTGCCGTGATGTCTTCTCCTCCCATCTAGTAGTAGTAGGCGGCCGCTC
TAGAGGATCCAAGCTTACGTACGCGTGCATGCGACGTCATAGCTCTTCTATAGTGTC
ACCTAAATTCAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGG
CGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAG
CGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTTGCGCAGCCTGAATGGCGAA
TGGGACGCGCCCTGTAGCGGCGCATTAAACCGCGGCGGGTGTGGGTGGGTTACGCC
CACGTGACCCGCTACACTTGCCAGCGCCCTANCGCCCCGCTCCTTTCGCTTTCTTTCC
CTTCCTTTCTCGNCACGTTTCGGCCGNTTTTCCCCGTCAAGCTCTTAAATCGGGGGG
CTTCCCTTTAAGGGTTNCCGAATTANTGCTTTACCGGNACCCTTGACCCCCAAAAAA
ACTTGGANTAAGGGGNGATGGNTCNCGTAANTGGGGGCCATCNCCCCTGAANAGA
ACGGTTTTTCNCCCCTTTTGACNGTTGGGNGTTCCNCGGTTTTTAAAAAANGGGACC
TTTTNTTTCCAAAACTGGGAANANACCTAAACCCTATTTTTGGGGCTATTTTTTTGAN
TTTNAAANGGGATTTTGCCCCATTTTNGGCCCTNTTGGGGTAAAAAAAAGAGCCGG
TTTTAAAAAAAATTTTACCCCAAATTTTAACAAAAATTTTTT
Translation:
LRWCIPSGELCFRSDHIGCCSGKCAFVCL (SEQ ID NO:267)
Toxin Sequence:
Leu-Arg-Xaa4-Cys-Ile-Xaa3-Ser-Gly-Xaa1-Leu-Cys-Phe-Arg-Ser-Asp-His-Ile-Gly-Cys-Cys- (SEQ ID NO:268)
Ser-Gly-Lys-Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
Name: δStriatus 26
Species: striatus
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAGATGGTGCATTCCTAGTGGTGATCTTTGTTTCCGCTCGGATCACATAGGATGC (SEQ ID NO:269)
TGCAGTGGCAAGTGCGCATTCGTCTGCTTGTAA
Translation:
LRWCIPSGDLCFRSDHIGCCSGKCAFVCL (SEQ ID NO:270)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Arg-Ser-Asp-His-Ile-Gly-Cys-Cys-Ser-Gly-Lys- (SEQ ID NO:271)
Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
Name: δStriatus 106
Species: striatus
Isolated: No
Cloned: Yes
DNA Sequence:
TTGAGATGGTGCATTCCTAGTGGTGATCTTTGTTTCCGCTCGGATCACATACAATGC (SEQ ID NO:272)
TGCAGTGGCAAGTGCGCATTCGTCTGCTTGTAA
Translation:
LRWCIPSGDLCFRSDHIQCCSGKCAFVCL (SEQ ID NO:273)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Arg-Ser-Asp-His-Ile-Gln-Cys-Cys-Ser-Gly-Lys- (SEQ ID NO:274)
Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
Name: O6.3
Species: obscurus
Isolated: No
Cloned: Yes
DNA Sequence:
cgatccatctgtccatccatccattcagtcattcgctgccaaactgtaacaaatattcaagtcttgctttctgtttgtgtctgaca (SEQ ID NO:275)
gATTGAGATGGTGCGTTCCTAGCGGTGAAGTTTGTCGCCGCTATGAATTCGTGGGATGCTGCAG
TGGCAAGTGCTTCTTCGTCTGCTCGTAAAACTGTTGTGATGTCTTCTCCTCCCCTC
Translation:
VSDRLRWCVPSGEVCRRYEFVGCCSGKCFFVCS (SEQ ID NO:276)
Toxin Sequence:
Leu-Arg-Xaa4-Cys-Val-Xaa3-Ser-Gly-Xaa1-Val-Cys-Arg-Arg-Xaa5-Xaa1-Phe-Val-Gly-Cys- (SEQ ID NO:277)
Cys-Ser-Gly-Lys-Cys-Phe-Phe-Val-Cys-Ser-{circumflex over ( )}
Name: R6.3
Species: radiatus
Isolated: No
Cloned: Yes
DNA Sequence:
ctctctctctctctgctggacaggTCGACTCGCTGCTTGCCTGACGGAACGTCTTGCCTTTTTAGTA (SEQ ID NO:278)
GGATCAGATGCTGCGGTACTTGCAGTTCAATCTTAAAGTCATGTGTGAGCTGATCCG
GCGGTTGATCTTCCTCCCTCTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTG
AGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACAT
TGAAATAAAAGCCGCATTGC
Translation:
RSTRCLPDGTSCLFSRIRCCGTCSSILKSCVS (SEQ ID NO:279)
Toxin Sequence:
Cys-Leu-Xaa3-Asp-Gly-Thr-Ser-Cys-Leu-Phe-Ser-Arg-Ile-Arg-Cys-Cys-Gly-Thr-Cys-Ser-Ser- (SEQ ID NO:280)
Ile-Leu-Lys-Ser-Cys-Val-Ser-{circumflex over ( )}
Name: G6.3
Species: geographus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCTTGCACGGTGAATTTCGCTTCATATTTTTCTACTGTCGTCTTTGGCATCATCC (SEQ ID NO:281)
AAAACATCACCAAGATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGA
CCGCCTGGACATTCGTCACGGCTGTGCCTCACTCCAGCGATGTATTGGAGAATCTTT
ATCTGAAGGCACTTCACGAAACGGAAAACCACGAAGCCTCTAAATTGAACGTGAGA
GACGACGAGTGCGAACCTCCTGGAGATTTTTGTGGCTTTTTTAAAATTGGGCCGCCT
TGCTGCAGTGGCTGGTGCTTCCTCTGGTGCGCCTAAAACTGCCGTGATGTCTTCTATT
CCCCTCTGTGCTACCTGGCTTGATCTTTGATTGGCGCGTGCCCTTCAGTGGTTATGAA
CCCCCCTGAGCCGACTCTCTGGGGGCCTCGGGGGTTCAACATCCAAATAAAGCGAC
AACACAATCACAAGTAAAAAA
Translation:
MKLTCMMIVAVLFLTAWTFVTAVPHSSDVLENLYLKALHETENHEASKLNVRDDECEP (SEQ ID NO:282)
PGDFCGFFKIGPPCCSGWCFLWCA
Toxin Sequence:
Asp-Asp-Xaa1-Cys-Xaa1-Xaa3-Xaa3-Gly-Asp-Phe-Cys-Gly-Phe-Phe-Lys-Ile-Gly-Xaa3-Xaa3- (SEQ ID NO:283)
Cys-Cys-Ser-Gly-Xaa4-Cys-Phe-Leu-Xaa4-Cys-Ala-{circumflex over ( )}
Name: Tx6.8
Species: textile
Isolated: No
Cloned: Yes
DNA Sequence:
GCTGCAGGTCGACTCTAGAGGCGTTGGAGAATCTTTATCTGAAGGCACATCATGAA (SEQ ID NO:284)
ATGAACAACCCCGAAGACTCTGAATTGAACAAGAGGTGCTATGATAGTGGGACAAG
TTGTAACACTGGAAACCAATGCTGCAGTGGCTGGTGCATTTTCGTCTGCCTCTAAAA
CTGCCGTGATGTCTTCTACTCCCCTCTGTGCTACCTACCTGGCTTGATCTTTGATTGG
CGCGTGCCCTTCACTGGTTATGAACCCCTCTGATCCGACTCTCTGGGGGCCTCGGGG
ATCCAACATCAAAATANAGCGACAGCACAATCAC
Translation:
CRSTLEALENLYLKAHHEMNNPEDSELNKRCYDSGTSCNTGNQCCSGWCIFVCL (SEQ ID NO:285)
Toxin Sequence:
Cys-Xaa5-Asp-Ser-Gly-Thr-Ser-Cys-Asn-Thr-Gly-Asn-Gln-Cys-Cys-Ser-Gly-Xaa4-Cys-Ile- (SEQ ID NO:286)
Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Qc6.1
Species: quercinus
Isolated: No
Cloned: Yes
DNA Sequence:
GCTTCGTATTTCTCCGCTGTCTTCCTTGGCATCACCCAAAACATCACCAAGATGAAA (SEQ ID NO:287)
CTGACGTGCATGATGATCGTTGCTCTGCTGTTCTTGACCGCCTGGACATTCGTCACG
GCTGTTGACTCCAAAAATGAACTGGAGaACAGAGGAGGATGGGGGCAGGCAGGAG
GATGGGGGAAACTTTTTCCGATGGCACGCGACGAAATGAAAAACAGCGAAGTCTCT
AAATTGGACAATAAGAGAAAGTGCGCTGCAGCCGGTGAAGCTTGCGTAATACCTAT
CATTGGaAACGTATTTTGCTGCAAAGGCTACTGtCTTTTCGTCTGCATTAGTTAAACT
GcTGTGATGCcTTCTACTCACCTCTGTGCTACCTGGCTTGATCTTTGATTGGCGTGTGC
CCTTCACTGGTTATGAgCTCGTCTGAtCCTACTCTCTGGAGACCTCTGTGGTCCAACAt
CCaAATAAAGCGGcATCCCAATG
Translation:
MKLTCMMIVALLFLTAWTFVTAVDSKNELENRGGWGQAGGWGKLFPMARDEMKNSE (SEQ ID NO:288)
VSKLDNKRKCAAAGEACVIPIIGNVFCCKGYCLFVCIS
Toxin Sequence:
Cys-Ala-Ala-Ala-Gly-Xaa1-Ala-Cys-Val-Ile-Xaa3-Ile-Ile-Gly-Asn-Val-Phe-Cys-Cys-Lys-Gly- (SEQ ID NO:289)
Xaa5-Cys-Leu-Phe-Val-Cys-Ile-Ser-{circumflex over ( )}
----------
Name: Lp6.5
Species: leopardus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGGATATTC (SEQ ID NO:290)
ATCACGGCTGATGACTCCACAAATGGACTGGAGAATCGTTTTAGGAAGGCACGTGA
CAACATGAAGAACGCCAAAGCCTCTACATTAGCCGAGAAGAAAGCGTGTGTTGAAC
TTGGTGAGATTTGTGCCACAGGCTTCTTCCTAGACGAGGAATGCTGCACTGGTTCAT
GCCATGTCTTCTGCGTACTATAGTTAAACTGCTGTGATGTCTTCTTCTCTCCTCCGTG
CTACCTGGCTTGATCTTTGATTGGTGCCTGTCCTTCAGTGGTTGTGAAACCCTCTGAT
CCTACTCTCTGGACGCCTCTGAGGCCCAACATCCAAATAAAGCGACATCCTAATGCC
AAAAAAAAAAA
Translation:
MKLTCVVIVAVLFLTAWIFITADDSTNGLENRFRKARDNMKNAKASTLAEKKACVELG (SEQ ID NO:291)
EICATGFFLDEECCTGSCHVFCVL
Toxin Sequence:
Ala-Cys-Val-Xaa1-Leu-Gly-Xaa1-Ile-Cys-Ala-Thr-Gly-Phe-Phe-Leu-Asp-Xaa1-Xaa1-Cys-Cys- (SEQ ID NO:292)
Thr-Gly-Ser-Cys-His-Val-Phe-Cys-Val-Leu-{circumflex over ( )}
----------
Name: Mr6.4
Species: marmoreus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTT (SEQ ID NO:293)
GCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTTTCGAAGGCACATCA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCCCTAACACTGGTG
AATTATGTGATGTGGTTGAACAAAACTGCTGCTATACCTATTGCTTTATTGTAGTCT
GCCTATAAAACTACCGTGATGTCTTCTACTCCCCTCTGTGCTGCCTGGCTTGATCTTT
GATTGGCGCGTGCCCTTCACTGGTTATGACCCCCCTGATCCGACCTCTGGGG
Translation:
MKLTCVVIVAVLFLTAWTFATADDPRNGLENLFSKAHHEMKNPEASKLNKRCPNTGEL (SEQ ID NO:294)
CDVVEQNCCYTYCFIVVCL
Toxin Sequence:
Cys-Xaa3-Asn-Thr-Gly-Xaa1-Leu-Cys-Asp-Val-Val-Xaa1-Gln-Asn-Cys-Cys-Xaa5-Thr-Xaa5- (SEQ ID NO:295)
Cys-Phe-Ile-Val-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Qc6.2
Species: quercinus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTATGGTGATCGTTGCTGTGCTATTCTTGACCGCCTCG (SEQ ID NO:296)
GCTGATGACTCCAGAAATGGATTCGAGAATCGAAATGGAGAACGAAACGAAAACG
AAATGAAGAACCTCGAAGCCTCTAAATTGAACAGGAGAGACGGCGATTGCGTTGAT
GGTGGTGAATTTTGTGGCTTTCCGAAAATTGGAGGGCCATGCTGTAGTGGCTGGTGC
TTTTTCGTCTGCTTATAAAACTGCCATGATGTCTTCTACCCCCCTCTGTGCTACCTGA
CTTGATCTTTGATTGGCGTGTGCCCTTCACTGGTTATGAACCCCTCTGATCCGACTCT
CTGGAGGCCTCGGGGGTCCAACATCCAAATAAAGCGACAGCAAAAAAAAAAAAAA
AAAAAA
Translation:
MKLTCMVIVAVLFLTASADDSRNGFENRNGERNENEMKNLEASKLNRRDGDCVDGGE (SEQ ID NO:297)
FCGFPKIGGPCCSGWCFFVCL
Toxin Sequence:
Asp-Gly-Asp-Cys-Val-Asp-Gly-Gly-Xaa1-Phe-Cys-Gly-Phe-Xaa3-Lys-Ile-Gly-Gly-Xaa3-Cys- (SEQ ID NO:298)
Cys-Ser-Gly-Xaa4-Cys-Phe-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Qc6.3
Species: quercinus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTATTCTTGACCGCCTTG (SEQ ID NO:299)
GCTGATGACTCCAGAAATGGATTGGAGAATCGAAATGAACAAGAACGAAACGAAA
ACGAAATGAGGGACCGCCGGGACTGCCAAGATAGTGGTGTAGTTTGTGGCTTTCCG
AAACCTGAACCACACTGCTGCAGTGGCTGGTGCCTTTTCGTCTGCGCCTAAAACTGC
CGTGATGTCAAATAAAGCGACAGACAATNAAAAAAAAAAAAAAAAAAAA
Translation:
MKLTCVVIVAVLFLTALADDSRNGLENRNEQERNENEMRDRRDCQDSGVVCGFPKPEP (SEQ ID NO:300)
HCCSGWCLFVCA
Toxin Sequence:
Asp-Cys-Gln-Asp-Ser-Gly-Val-Val-Cys-Gly-Phe-Xaa3-Lys-Xaa3-Xaa1-Xaa3-His-Cys-Cys-Ser- (SEQ ID NO:301)
Gly-Xaa4-Cys-Leu-Phe-Val-Cys-Ala-{circumflex over ( )}
----------
Name: Ar6.5
Species: arenatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:302)
ACATTCGTCACGGCTGACTCCATACGTGCACTGGAGGATTTTTTTGCGAAGGCACGT
GACGAAATGGAAAACAGCGGAGCTTCTCCATTGAACGAGAGAGACTGCCGACCTGT
AGGTCAATATTGTGGCATACCGTATAAGCACAACTGGCGATGCTGCAGTCAGCTTTG
TGCAATTATCTGTGTTTCCTAACCCCTCTGATCCTACTCTCTGAAGACCTCCGGGATT
CAACATCCAAATAAAGCGACATCCCGATNAAAAAAAANGAAAAAAAAAAAAAAAA
Translation:
MKLTCVVIVAVLFLTAWTFVTADSIRALEDFFAKARDEMENSGASPLNERDCRPVGQY (SEQ ID NO:303)
CGIPYKHNWRCCSQLCAIICVS
Toxin Sequence:
Asp-Cys-Arg-Xaa3-Val-Gly-Gln-Xaa5-Cys-Gly-Ile-Xaa3-Xaa5-Lys-His-Asn-Xaa4-Arg-Cys- (SEQ ID NO:304)
Cys-Ser-Gln-Leu-Cys-Ala-Ile-Ile-Cys-Val-Ser-{circumflex over ( )}
----------
Name: Ar6.11
Species: arenatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTGTGGTGATCGTTGTTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:305)
ACATTCGTCAAGGCTGATGACTCCATAAATGGATTGGAGAATCTTTTTCCGAAGGCA
CGTCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACGAGAGGTGCCTTGAAAA
GGGTGTACTTTGTGATCCGAGTGCTGGAAACTGCTGTAGTGGCGAATGCGTTTTAGT
CTGCCTCTAAAACTACCGTGATGTCTTCTACTCCCATCTGTGCTACCCCTCGAG
Translation:
MKLTCVVIVVVLFLTAWTFVKADDSINGLENLFPKARHEMKNPEASKLNERCLEKGVL (SEQ ID NO:306)
CDPSAGNCCSGECVLVCL
Toxin Sequence:
Cys-Leu-Xaa1-Lys-Gly-Val-Leu-Cys-Asp-Xaa3-Ser-Ala-Gly-Asn-Cys-Cys-Ser-Gly-Xaa1-Cys- (SEQ ID NO:307)
Val-Leu-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Ar6.12
Species: arenatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCATGGTGATCGTTACTGTGTTGTTCTTGACCGCCTGG (SEQ ID NO:308)
ACATTCGTCACGGCTGATGACTCCAGAAATGAATTGGAGAATCTTTTTCTGAAGGCA
TATCACGAAATGAACTCCGAAGCCTCTAAATTGGACAAGAAAGAGTGCGTTGCTGG
TAGTCACTTTTGTGGTTTTCCGAAAATTGGAGGGCCATGCTGCAGTGGCTGGTGCTT
TTTCGTCTGCTTGTAAACCTGCCGTGATGTCTTCTACTCCCATCTGTGCTACCCCTCG
AG
Translation:
MKLTCMVIVTVLFLTAWTFVTADDSRNELENLFLKAYHEMNSEASKLDKKECVAGSHF (SEQ ID NO:309)
CGFPKIGGPCCSGWCFFVCL
Toxin Sequence:
Xaa1-Cys-Val-Ala-Gly-Ser-His-Phe-Cys-Gly-Phe-Xaa3-Lys-Ile-Gly-Gly-Xaa3-Cys-Cys-Ser- (SEQ ID NO:310)
Gly-Xaa4-Cys-Phe-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Ts6.2
Species: tessulatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTGTGGTGATCGTTGCTGTGATGTTCTTGACCGCCTGG (SEQ ID NO:311)
ACATTCATCACGGCTGATGACTCCATAAATGGACTGGAGGATAGAGGCATATGGGG
GGAACCTTTGTCGAAGGCACGTGACGAAATGAACCCCGAAGTCTCTAAACGGGATT
GCTGGCCTCAATATTGGTTTTGTGGCCTACAGAGGGGATGCTGCCCAGGGACTACTT
GCTTCTTCCTTTGCTTTTAGTGATCTCTTCGACTCCCTTCTGTGCTACCTGGCTTGACC
TTTGATTGGCGCGTGCCCTTCACTGGTTATAAACCCCTCTGTTCCTCCTCTCTGGACG
CTTCGGGGTGTCCAGCATCCAAATAAAGCGACGTCCCCAAAAAAAAAAAAAAAAA
AA
Translation:
MKLTCVVIVAVMFLTAWTFITADDSINGLEDRGIWGEPLSKARDEMNPEVSKRDCWPQ (SEQ ID NO:312)
YWFCGLQRGCCPGTTCFFLCF
Toxin Sequence:
Asp-Cys-Xaa4-Xaa3-Gln-Xaa5-Xaa4-Phe-Cys-Gly-Leu-Gln-Arg-Gly-Cys-Cys-Xaa3-Gly-Thr- (SEQ ID NO:313)
Thr-Cys-Phe-Phe-Leu-Cys-Phe-{circumflex over ( )}
----------
Name: Ts6.4
Species: tessulatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGGTCGTTGCTGTGCTGTTCTTGAACGCCTGG (SEQ ID NO:314)
ACATTCGCCACGGCTGTTGACTCCAAACATGCACTGGCGAAACTTTTTATGAAGGCA
CGTGACGAAATGTATAACCCCGATGCCACTAAATTGGACGATAAGAGATGGTGCGC
TTTAGATGGTGAACTTTGTATCATACCGGTCATTGGGTCCATATTTTGCTGCCATGGC
ATATGTATGATCTACTGCGTCTAGTTGAACTGCCGTGATGTCTTCTACTCCCCTCTGT
GCTACCCCTGGTTTGATCTTTGATTGCCCTGTGCCCTTCACTGATTATGAATCCCTCT
GATCCTACTCTCTGAAGACCTCTTGGGGTCCAACATCCAAATAAAGCGACATCCCAA
AAAAAAAAAAAAAAAAAA
Translation:
MKLTCVVVVAVLFLNAWTFATAVDSKHALAKLFMKARDEMYNPDATKLDDKRWCAL (SEQ ID NO:315)
DGELCIIPVIGSIFCCHGICMIYCV
Toxin Sequence:
Xaa4-Cys-Ala-Leu-Asp-Gly-Xaa1-Leu-Cys-Ile-Ile-Xaa3-Val-Ile-Gly-Ser-Ile-Phe-Cys-Cys- (SEQ ID NO:316)
His-Gly-Ile-Cys-Met-Ile-Xaa5-Cys-Val-{circumflex over ( )}
----------
Name: Im6.1
Species: imperialis
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGTTCGTTGCTGTGCCGTTCTTGACCGCCTCG (SEQ ID NO:317)
GTATTCATCACGGCTGATGACTCCAGAAATGGAATCGAGAATCTTCCTCGGATGAG
ACGTCACGAAATGAAGAACCCCAAAGCCTCTAAGTTGAACAAGAGACAGTGCCGTG
TAGAAGGTGAAATTTGTGGCATGCTGTTTGAAGCACAATGCTGCGATGGCTGGTGCT
TTTTCGTCTGCATGTAAAACTGCCGTGATGTCTTCTACTCTCCTCTGTGCTACCTGCC
CTGATCTTTGATTGGCTCGCGCCCTTCATTGGTTATGAACCCCTCTGATCCTACTCTC
TGGAGGCCTCAGGGGTCCAGCATCTAAATAAAGCGACATCACAATCAAAAAAAAA
AAAAAAAAAAA
Translation:
MKLTCVVFVAVPFLTASVFITADDSRNGIENLPRMRRHEMKNPKASKLNKRQCRVEGEI (SEQ ID NO:318)
CGMLFEAQCCDGWCFFVCM
Toxin Sequence:
Xaa2-Cys-Arg-Val-Xaa1-Gly-Xaa1-Ile-Cys-Gly-Met-Leu-Phe-Xaa1-Ala-Gln-Cys-Cys-Asp-Gly- (SEQ ID NO:319)
Xaa4-Cys-Phe-Phe-Val-Cys-Met-{circumflex over ( )}
----------
Name: Ca6.5
Species: caracteristicus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:320)
ACATTCGTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTTTTTCCGAAGGCA
CGTCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCGTTGACCC
TGGTGAATTTTGTGGTCCGGGATTTGGAGATTGCTGCACTGGCTTCTGCCTTTTAGTC
TGCATCTAAAACTGCCGTGATGTCTTCTACTCCCATCTGTGCTACCCCTCGAG
Translation:
MKLTCVVIVAVLFLTAWTFVTADDSRNGLENLFPKARHEMKNPEASKLNKRCVDPGEF (SEQ ID NO:321)
CGPGFGDCCTGFCLLVCI
Toxin Sequence:
Cys-Val-Asp-Xaa3-Gly-Xaa1-Phe-Cys-Gly-Xaa3-Gly-Phe-Gly-Asp-Cys-Cys-Thr-Gly-Phe-Cys- (SEQ ID NO:322)
Leu-Leu-Val-Cys-Ile-{circumflex over ( )}
----------
Name: Mf6.2
Species: miliaris
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCGTTGCTGTGTTGTTCTTGACCGCCTGG (SEQ ID NO:323)
ACATTCGTCATGGCTGATGACTCCAGAAATGATTTGGAGAATCTTTTTCTGAAGGCA
CGTCATGAAATGAAGAACCCCGAAGCTTCTAAATTGAACAAGAGATGCCTTCCAAA
TGGTGTACTTTGTGATCTGGGATCTCCACCATACTGCTGCAGTGGCTGGTGCGCGAT
CGTCGTCTGCATCTAAAACTGTCGTCATGTCTTCTACTCCCATCTGTGCTACCCCTCG
AG
Translation:
MKLTCVVIVAVLFLTAWTFVMADDSRNDLENLFLKARHEMKNPEASKLNKRCLPNGV (SEQ ID NO:324)
LCDLGSPPYCCSGWCAIVVCI
Toxin Sequence:
Cys-Leu-Xaa3-Asn-Gly-Val-Leu-Cys-Asp-Leu-Gly-Ser-Xaa3-Xaa3-Xaa5-Cys-Cys-Ser-Gly- (SEQ ID NO:325)
Xaa4-Cys-Ala-Ile-Val-Val-Cys-Ile-{circumflex over ( )}
----------
Name: Ak6.1
Species: atlanticus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:326)
ACATTCGTCACGGCTGATGACTCCATAAATGGGTTGGAGAATCTTTTTCCGAAGGCA
CGTCACGAAATGAGGAAACCCGAAGCCTCTAGATCGAGAGGGAGGTGCCGTCCTCG
TGGTATGTTCTGTGGCTTTCCGAAACCTGGACCATACTGCTGCAATGGCTGGTGCTT
TTTCGTCTGCATCTAAAACTGCCGTGATGTGTTCTACTCCCATCTGTGCTACCCCTCG
AG
Translation:
MKLTCVVIVAVLFLTAWTFVTADDSNGLENLFPKARHEMRKPEASRSRGRCRPRGMF (SEQ ID NO:327)
CGFPKPGPYCCNGWCFFVCI
Toxin Sequence:
Cys-Arg-Xaa3-Arg-Gly-Met-Phe-Cys-Gly-Phe-Xaa3-Lys-Xaa3-Gly-Xaa3-Xaa5-Cys-Cys-Asn- (SEQ ID NO:328)
Gly-Xaa4-Cys-Phe-Phe-Val-Cys-Ile-{circumflex over ( )}
----------
Name: Lv6.1
Species: lividus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:329)
ACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGAGAATCTTTTTTCGAAGGCA
CATCACGAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGGTGCCCTAACAC
TGGTGAATTATGTGATGTGGTTGAACAAAACTGCTGCTATACCTATTGCTTTATTGT
AGTCTGCCTATAAAACTACCGTGATGTCTTCTACTCCCATCTGTGCTACCCCTCGAG
Translation:
MKLTCVVIVAVLFLTAWTFATADDPRNGLENLFSKAHHEMKNPEASKLNKRCPNTGEL (SEQ ID NO:330)
CDVVEQNCCYTYCFIVVCL
Toxin Sequence:
Cys-Xaa3-Asn-Thr-Gly-Xaa1-Leu-Cys-Asp-Val-Val-Xaa1-Gln-Asn-Cys-Cys-Xaa5-Thr-Xaa5- (SEQ ID NO:331)
Cys-Phe-Ile-Val-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Pu6.3
Species: pulicarius
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCATGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:332)
ACATTCGTCAAGGCTGATGACTCCAGAAATGGATTGGAGAATCTTTTTCCGAAGGC
ACGTCACGAAATGAAGAACTCCAAAGCCTCTAAATTAAACAAGAGGTGCGTTGAAG
ATGGTGATTTTTGTGGTCCGGGATATGAAGAGTGCTGCAGTGGCTTCTGCCTTTACG
TCTGCATCTAAAACTGCCGTGATGTCTTCTACTCCCATCTGTGCTACCCCTCGAG
Translation:
MKLTCMVIVAVLFLTAWTFVKADDSRNGLENLFPKARHEMKNSKASKLNKRCVEDGD (SEQ ID NO:333)
FCGPGYEECCSGFCLYVCI
Toxin Sequence:
Cys-Val-Xaa1-Asp-Gly-Asp-Phe-Cys-Gly-Xaa3-Gly-Xaa5-Xaa1-Xaa1-Cys-Cys-Ser-Gly-Phe- (SEQ ID NO:334)
Cys-Leu-Xaa5-Val-Cys-Ile-{circumflex over ( )}
----------
Name: Ge6.1
Species: generalis
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGTGTGGTGATCGTTGCTGTGCTATTCTTGACCGCCTGG (SEQ ID NO:335)
ACATTCGTCACGGCTGATGACACCAGATATAAACTGGAGAATCCTTTTCTGAAGGC
ACGCAACGAACTGCAGAAACACGAAGCCTCTCAACTGAACGAGAGAGGCTGCCTTG
ACCCAGGTTACTTCTGTGGGACGCCGTTTCTTGGAGCATACTGCTGCGGTGGCATTT
GCCTTATTGTCTGCATAGAAACGTAAAGGCTTGATGTCTTCTACTCCCATCTGTGCT
ACCCCTCGAG
Translation:
MKLTCVVIVAVLFLTAWTFVTADDTRYKLENPFLKARNELQKHEASQLNERGCLDPGY (SEQ ID NO:336)
FCGTPFLGAYCCGGICLIVCIET
Toxin Sequence:
Gly-Cys-Leu-Asp-Xaa3-Gly-Xaa5-Phe-Cys-Gly-Thr-Xaa3-Phe-Leu-Gly-Ala-Xaa5-Cys-Cys- (SEQ ID NO:337)
Gly-Gly-Ile-Cys-Leu-Ile-Val-Cys-Ile-Xaa1-Thr-{circumflex over ( )}
----------
Name: Ep6.1
Species: episcopatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCGTTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:338)
ACATTTGCCACGGCTGATGACCCCAGAAATGGATTGGGGAATCTTTTTTCGAATGTA
CATCACGAAATGAAGAACCTCGAAGACTCTAAATTGGACAAGAAGTGCCTTGGGTT
TGGTGAAGCTTGTCTTATGCTTTATTCAGACTGCTGCAGCTATTGCGTTGCTCTTGTC
TGCCTATAAAACTACCGTGACGTCTTCTACTCCCCTCTGTGCTACCTGGCTTGATCTT
TGATTGGCGTGTGCGCTTCACTGGTTATGAACCCCTCTGATCCTACTCTCTGAAGAC
CTCTGGGGTCCAACATCCAAATAAAGCGACATCACAAAAAAAAAAAAAAAAAAAA
AA
Translation:
MKLTCVVIVAVLFLTAWTFATADDPRNGLGNLFSNVHHEMKNLEDSKLDKKCLGFGEA (SEQ ID NO:339)
CLMLYSDCCSYCVALVCL
Toxin Sequence:
Cys-Leu-Gly-Phe-Gly-Xaa1-Ala-Cys-Leu-Met-Leu-Xaa5-Ser-Asp-Cys-Cys-Ser-Xaa5-Cys-Val- (SEQ ID NO:340)
Ala-Leu-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Ep6.2
Species: episcopatus
Isolated: No
Cloned: Yes
DNA Sequence:
GGATCCATGAAACTGACGTGCGTGGTGATCATTGCTGTGCTGTTCTTGACCGCCTGG (SEQ ID NO:341)
ACATTCGTCATGGCTGATGACCCCAGAGATGAACCGGAGGCACGTGACGAAATGAA
CCCCGCAGCCTCTAAATTGAACGAGAGAGGCTGCCTTGCAGTTGATTATTTTTGCGG
CATACCGTTTGTGAGCAACGGGCTATGCTGCAGTGGCAATTGTGTTTTTGTCTGCAC
ACCCCAAGGGAAGTAAAACTGCCGTGACGTCTTCTACTCCCCTCTGTGCTACCTGGC
TTGATCTTTGATTGGCGTGTGCACTTCACTGGTTATGAACCCCTCTGATCCTACTCTC
TGAAGACCTCTGGGGTCCAACATCCAAATAAAGCGACATCCCAAAAAAAAAAAAA
AAAAAAA
Translation:
MKLTCVVIIAVLFLTAWTFVMADDPRDEPEARDEMNPAASKLNERGCLAVDYFCGIPFV (SEQ ID NO:342)
SNGLCCSGNCVFVCTPQGK
Toxin Sequence:
Gly-Cys-Leu-Ala-Val-Asp-Xaa5-Phe-Cys-Gly-Ile-Xaa3-Phe-Val-Ser-Asn-Gly-Leu-Cys-Cys- (SEQ ID NO:343)
Ser-Gly-Asn-Cys-Val-Phe-Val-Cys-Thr-Xaa3-Gln-#
----------
Name: Ac6.1
Species: achatinus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCTCTGTCCTCCATCTATTATTATTCGCTGCCAAACTGTGTTAAATATTCAAGT (SEQ ID NO:344)
CTCTCTTTCTGTTTGTGTCTAACAGGTTGAGATGGTGCATTCCTAGAGGTGATCTTTG
TTTCCCCTCGGATCGCATACAATGCTGCAGTGGCAAGTGCACATTCGTCTGCATGTA
AAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
LRWCIPRGDLCFPSDRIQCCSGKCTFVCM (SEQ ID NO:345)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Arg-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-Arg-Ile-Gln-Cys-Cys-Ser-Gly- (SEQ ID NO:346)
Lys-Cys-Thr-Phe-Val-Cys-Met-{circumflex over ( )}
----------
Name: Ac6.2
Species: achatinus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCTCTGTCCTCCTCCTTCATTCATTCGCTGCCAAACTGTATTAAATATTCGAAT (SEQ ID NO:347)
CTCTCTTTCTGTTTGTGTCTGACAGATTGAGAGGGTGCGTTCCTAGTGGTGAAATTTG
TTACTTCATGGATCACATAGGATGCTGCAGTGGCAAGTGCACATTCGTCTGCATGTA
AAACTGCCGTGATGTCTTCTCCTCCCATC
Translation:
LRGCVPSGEICYFMDHIGCCSGKCTFVCM (SEQ ID NO:348)
Toxin Sequence:
Gly-Cys-Val-Xaa3-Ser-Gly-Xaa1-Ile-Cys-Xaa5-Phe-Met-Asp-His-Ile-Gly-Cys-Cys-Ser-Gly- (SEQ ID NO:349)
Lys-Cys-Thr-Phe-Val-Cys-Met-{circumflex over ( )}
----------
Name: Bu6.7
Species: bullatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTACTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:350)
GTCACGGCTGATGACTCCACATATGGATTGAAGAATCTTTTGCCGAACGGACGTCAT
GAAATGATGAACCCCGAAGCCCCTAAATTGAACAAGAAAGATGAATGCTCTGCTCC
TGGTGCATTTTGTCTCATCAGGCCAGGACTCTGCTGCAGCGAGTTCTGCTTCTTTGCG
TGTTTTTAGTGACGGTTGATGTCTTCTACTCCCCTC
Translation:
MKLTCVMIVTVLFLTAWTFVTADDSTYGLKNLLPNGRHEMMNPEAPKLNKKDECSAP (SEQ ID NO:351)
GAFCLIRPGLCCSEFCFFACF
Toxin Sequence:
Asp-Xaa1-Cys-Ser-Ala-Xaa3-Gly-Ala-Phe-Cys-Leu-Ile-Arg-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:352)
Phe-Cys-Phe-Phe-Ala-Cys-Phe-{circumflex over ( )}
----------
Name: Bu6.8
Species: bullatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTACTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:353)
GTCACGGCTGATGACTCCAGAGACGCTCCGGATAGTGCAGAAGGATGGGAGAAACT
TTTCTCGGAGGCACGTGACGAAATGAAGAACCGCAAAGACTTTGAATTGAGAGGGT
GCCTTCCTAGGTGGGAATTTTGTCCCATCTTTAAAAAAAACGATTGCTGCAGTGGCA
TATGCATAAGCATCTGCTTGTAAAACTCCGTGATGTCTTCTCTTCCCATC
Translation:
MKLTCVMIVTVLFLTAWTFVTADDSRDAPDSAEGWEKLFSEARDEMKNRKDFELRGCL (SEQ ID NO:354)
PRWEFCPIFKKNDCCSGICISICL
Toxin Sequence:
Gly-Cys-Leu-Xaa3-Arg-Xaa4-Xaa1-Phe-Cys-Xaa3-Ile-Phe-Lys-Lys-Asn-Asp-Cys-Cys-Ser-Gly- (SEQ ID NO:355)
Ile-Cys-Ile-Ser-Ile-Cys-Leu-{circumflex over ( )}
----------
Name: Sx6.4
Species: striolatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATTGTTGCTGTGCTGTTCTTGACCGCCTGGATATTT (SEQ ID NO:356)
GTAATGGCTGATGACTCCAGAAATGGATTGGAGAATCTTCCTCAGACTACACGTCA
CGAAATGAAGAACCCCGAAGCCTCTAAATTGAACCAGACAGACTGCCTTGCTAAAG
ACGCTTTCTGTGCCTGGCCGATACTTGGACCACTGTGCTGCAGTCGCTTGTGCTTAT
ACGTCTGCATGtaaAACTGCCGTGATGTCTTCTACTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWIFVMADDSRNGLENLPQTTRHEMKNPEASKLNQTDCLAKD (SEQ ID NO:357)
AFCAWPILGPLCCSRLCLYVCM
Toxin Sequence:
Asp-Cys-Leu-Ala-Lys-Asp-Ala-Phe-Cys-Ala-Xaa4-Xaa3-Ile-Leu-Gly-Xaa3-Leu-Cys-Cys-Ser- (SEQ ID NO:358)
Arg-Leu-Cys-Leu-Xaa5-Val-Cys-Met-{circumflex over ( )}
----------
Name: Cn6.9
Species: consors
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:359)
GTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTTTCTCCGAAGGCACGTCA
CGAAATGAAGAACCCCGAAGCCTCTAAATCGAACAAGAGATATGAGTGCTATTCTA
CTGGTACATTTTGTGGCATCAACGGAGGACTCTGCTGCAGCAACCTTTGCTTATTTTT
CGTGTGCTTAACATTTTCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRNGLENLSPKARHEMKNPEASKSNKRYECYST (SEQ ID NO:360)
GTFCGINGGLCCSNLCLFFVCLTFS
Toxin Sequence:
Xaa5-Xaa1-Cys-Xaa5-Ser-Thr-Gly-Thr-Phe-Cys-Gly-Ile-Asn-Gly-Gly-Leu-Cys-Cys-Ser-Asn- (SEQ ID NO:361)
Leu-Cys-Leu-Phe-Phe-Val-Cys-Leu-Thr-Phe-Ser-{circumflex over ( )}
----------
Name: Cn6.10
Species: consors
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCCTGATGATCGTTGCTGTGCTGTTCTTGACCACCTGGACATTC (SEQ ID NO:362)
GTCACGGCTGATGACTCCAGATATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCTGAAGCCTCTAAATTGAACAAGAGAGATGGGTGCTATAATGC
TGGTACATTTTGTGGCATCCGTCCAGGACTCTGCTGCAGCGAGTTTTGCTTTTTATGG
TGCATAACATTTGTTGATTCTGGCTAACAGTGTGCGTTGGTTGATGTCTTCTACTCCC
CTC
Translation:
MKLTCLMIVAVLFLTTWTFVTADDSRYGLKNLFPKARHEMKNPEASKLNKRDGCYNA (SEQ ID NO:363)
GTFCGIRPGLCCSEFCFLWCITFVDSG
Toxin Sequence:
Asp-Gly-Cys-Xaa5-Asn-Ala-Gly-Thr-Phe-Cys-Gly-Ile-Arg-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1- (SEQ ID NO:364)
Phe-Cys-Phe-Leu-Xaa4-Cys-Ile-Thr-Phe-Val-Asp-Ser-#
----------
Name: Cr6.6
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGCCAAACTGTATTAAATATTC (SEQ ID NO:365)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTAGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAATGCCAAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTCTTCCCTC
Translation:
NRLSRCIPSGDLCFPSDHIQCCNAKCAFVCL (SEQ ID NO:366)
Toxin Sequence:
Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Asn-Ala-Lys-Cys- (SEQ ID NO:367)
Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.5
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGTCAAACTGTATTAAATATTC (SEQ ID NO:368)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTTGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAGTGCCAAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTACTCCCCTC
Translation:
NRLSWCIPSGDLCFPSDHIQCCSAKCAFVCL (SEQ ID NO:369)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Ser-Ala- (SEQ ID NO:370)
Lys-Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.5A
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGTCAAACTGTATTAAATATTC (SEQ ID NO:371)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTAGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAGTGCCAAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
NRLSRCIPSGDLCFPSDHIQCCSAKCAFVCL (SEQ ID NO:372)
Toxin Sequence:
Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Ser-Ala-Lys-Cys- (SEQ ID NO:373)
Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
Name: Cr6.6A
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGCCAAACTGTATTAAATATTC (SEQ ID NO:374)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTAGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAATGCCGAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
NRLSRCIPSGDLCFPSDHIQCCNAECAFVCL (SEQ ID NO:375)
Toxin Sequence:
Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Asn-Ala-Xaa1- (SEQ ID NO:376)
Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.5B
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGTCAAACTGTATTAAATATTC (SEQ ID NO:377)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTTGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACGATGCTGCAGTGCCAAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTCTTCCCATC
Translation:
NRLSWCIPSGDLCFPSDHIRCCSAKCAFVCL (SEQ ID NO:378)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Arg-Cys-Cys-Ser-Ala- (SEQ ID NO:379)
Lys-Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.6B
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGCCAAACTGTATTAAATATTC (SEQ ID NO:380)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTAGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAATGCCAAGTGCGCATTCGCCTGCT
TGTAAAACTGCCGTGATGTCTTCTCTTCCCCTC
Translation:
NRLSRCIPSGDLCFPSDHIQCCNAKCAFACL (SEQ ID NO:381)
Toxin Sequence:
Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Asn-Ala-Lys-Cys- (SEQ ID NO:382)
Ala-Phe-Ala-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.6C
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCATCTGTCCATCCATCTATTCATTCATTCGCTGCCAAACTGTATTAAATATTC (SEQ ID NO:383)
AAGTCTCTCTTTCTGTTTGTGTCTAACAGATTGAGTTGGTGCATTCCTAGTGGTGATC
TTTGTTTCCCCTCGGATCACATACAATGCTGCAATGCCAAGTGCGCATTCGTCTGCTT
GTAAAACTGCCGTGATGTCTTCTACTCCCCTC
Translation:
NRLSWCIPSGDLCFPSDHIQCCNAKCAFVCL (SEQ ID NO:384)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-IIe-Gln-Cys-Cys-Asn-Ala- (SEQ ID NO:385)
Lys-Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Cr6.7
Species: circumcisus
Isolated: No
Cloned: Yes
DNA Sequence:
CGATCCTCTGTCCTCCTCTATTATTATTCGCTGCCAACTGTATTAAATATTCAAGTCT (SEQ ID NO:386)
CTCTTTCTGTTTGTGTCTAACAGATTGAGTTGGTGCATTCCTACTGGTGATCTTTGTT
TCCCCTCGGATCACATACAATGCTGCAGTGGCAAGTGCACATTCGTCTGCATGTAAA
ACTGCCGTGATGTCTTCTCCTCCCCTC
Translation:
NRLSWCIPTGDLCFPSDHIQCCSGKCTFVCM (SEQ ID NO:387)
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Thr-Gly-Asp-Leu-Cys-Phe-Xaa3-Ser-Asp-His-Ile-Gln-Cys-Cys-Ser-Gly- (SEQ ID NO:388)
Lys-Cys-Thr-Phe-Val-Cys-Met-{circumflex over ( )}
----------
Name: Mn6.3
Species: monachus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:389)
GTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTTTCTCCGAAGGCACGTCA
CGAAATGAAGAACCCCGAAGCCTCTAAATCGAACAAGAGATATGAGTGCTATTCTA
CTGGTACATTTTGTGGCATCAACGGAGGACTCTGCTGCAGCAACCTTTGCTTATTTTT
CGTGTGCTTAACATTTTCGTGATGTCTTCTCCTCCCCTC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSRNGLENLSPKARHEMKNPEASKSNKRYECYST (SEQ ID NO:390)
GTFCGINGGLCCSNLCLFFVCLTFS
Toxin Sequence:
Xaa5-Xaa1-Cys-Xaa5-Ser-Thr-Gly-Thr-Phe-Cys-Gly-Ile-Asn-Gly-Gly-Leu-Cys-Cys-Ser-Asn- (SEQ ID NO:391)
Leu-Cys-Leu-Phe-Phe-Val-Cys-Leu-Thr-Phe-Ser-{circumflex over ( )}
----------
Name: Sm6.5
Species: stercusmuscarum
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATGATGATCGTTGCTGTGCTGTTCTTGACCGCCTGGACATTC (SEQ ID NO:392)
GTCACAGCTGATGACTCCATAAATGGACCGGAGAATAGACGAATATGGGAGAAACT
TTTGTTGAAGGCACGTGACGAAATGAAGAACCCCGAAGCCTCTCAATTGAGATGGT
GCATTCCTAGTGGTGAACTTTGTTTCCGCTCGGATCACATACAATGCTGCAGTGCCA
AGTGCGCATTCGTCTGCTTGTAAAACTACCGTGATGTCTTCTCCTCCCATC
Translation:
MKLTCMMIVAVLFLTAWTFVTADDSINGPENRRIWEKLLLKARDEMKNPEASQLRWCI (SEQ ID NO:393)
PSGELCFRSDHIQCCSAKCAFVCL
Toxin Sequence:
Xaa4-Cys-Ile-Xaa3-Ser-Gly-Xaa1-Leu-Cys-Phe-Arg-Ser-Asp-His-Ile-Gln-Cys-Cys-Ser-Ala- (SEQ ID NO:394)
Lys-Cys-Ala-Phe-Val-Cys-Leu-{circumflex over ( )}
----------
Name: Sm6.6
Species: stercusmuscarum
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTGTGATGATCGTTGCTGTGCTGTTCTTGATCGCCTGGACATTC (SEQ ID NO:395)
GTCACGGCTGATGACTCCAGAAATGGATTGAAGAATCTTTTTCCGAAGGCACGTCAT
GAAATGAAGAACCCCGAAGCCTCTAAATTGAACAAGAGAGATGGGTGCTCTAGTGG
TGGTACATTTTGTGGCATCCGTCCAGGACTCTGCTGCAGCGAGTTTTGCTTTCTTTGG
TGCATAACATTTATTGATTGATGTCTTCTATTCCCCTC
Translation:
MKLTCVMIVAVLFLIAWTFVTADDSRNGLKNLFPKARHEMKNPEASKLNKRDGCSSGG (SEQ ID NO:396)
TFCGIRPGLCCSEFCFLWCITFID
Toxin Sequence:
Asp-Gly-Cys-Ser-Ser-Gly-Gly-Thr-Phe-Cys-Gly-Ile-Arg-Xaa3-Gly-Leu-Cys-Cys-Ser-Xaa1-Phe- (SEQ ID NO:397)
Cys-Phe-Leu-Xaa4-Cys-Ile-Thr-Phe-Ile-Asp-{circumflex over ( )}
----------
Name: Sx6.5
Species: striolatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCATAATGACCGTTGCTGTGCTGTTCTTGACCGCTTGGACATTC (SEQ ID NO:398)
GTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTTCTTCTGAAGACACGTCA
CGAAGTGGAAAACCCCAAAGCCTCTAGGTCGGGCGGTAGGTGCCGTCCTGGTGGTA
CGGTTTGTGGCTTTCCGAAACCTGGACCATACTGCTGCAGTGGCTGGTGCTTTTTTGT
CTGCGCCTAAACCTGCCGTGATGTCTTCTCCTCCCATC
Translation:
MKLTCIMTVAVLFLTAWTFVTADDSRNGLENLLLKTRHEVENPKASRSGGRCRPGGTV (SEQ ID NO:399)
CGFPKPGPYCCSGWCFFVCA
Toxin Sequence:
Cys-Arg-Xaa3-Gly-Gly-Thr-Val-Cys-Gly-Phe-Xaa3-Lys-Xaa3-Gly-Xaa3-Xaa5-Cys-Cys-Ser- (SEQ ID NO:400)
Gly-Xaa4-Cys-Phe-Phe-Val-Cys-Ala-{circumflex over ( )}
----------
Name: Sx6.6
Species: striolatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGCGTGATGATCGTTGCTGTGCTGTTCTTGACTGCCTGGACATTC (SEQ ID NO:401)
GTCACGGCTGATGACTCCAAAAATGGACTGGAGAATCATTTTTGGAAGGCACGTGA
CGAAATGAAGAACCGCGAAGCCTCTAAATTGGACAAAAAGGAAGCCTGCTATCCGC
CTGGTACTTTTTGTGGCATAAAGCCCGGGCTATGCTGCAGTGAGTTGTGTTTACCGG
CCGTCTGCGTCGGTGGTTAACTGCCGTGATGTCTTCTATTCCCCTC
Translation:
MKLTCVMIVAVLFLTAWTFVTADDSKNGLENHFWKARDEMKNREASKLDKKEACYPP (SEQ ID NO:402)
GTFCGIKPGLCCSELCLPAVCVGG
Toxin Sequence:
Xaa1-Ala-Cys-Xaa5-Xaa3-Xaa3-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa3-Gly-Leu-Cys-Cys-Ser- (SEQ ID NO:403)
Xaa1-Leu-Cys-Leu-Xaa3-Ala-Val-Cys-Val-Gly-#
---------
Name: Sx6.7
Species: striolatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTCTGATGGCTGTTGCTGTGCTGTTCTTGACCGCCCGGACATTC (SEQ ID NO:404)
GTCACGGCTGATGACTCCAGAAATGGATTGGAGAATCTTTCTCCGAAGGCACGTCA
CGAAATGAAGAACCCCGAAGCCTCTAAATCGAACAAGAGATATGAGTGCTATTCTA
CTGGTACATTTTGTGGCATCAACGGAGGACTCTGCTGCAGCAACCTTTGCTTATTTTT
CGTGTGCTTAACATTTTCGTGATGTCTTCTATCCCCTC
Translation:
MKLTCLMAVAVLFLTARTFVTADDSRNGLENLSPKARHEMKNPEASKSNKRYECYSTG (SEQ ID NO:405)
TFCGINGGLCCSNLCLFFVCLTFS
Toxin Sequence:
Xaa5-Xaa1-Cys-Xaa5-Ser-Thr-Gly-Thr-Phe-Cys-Gly-Ile-Asn-Gly-Gly-Leu-Cys-Cys-Ser-Asn- (SEQ ID NO:406)
Leu-Cys-Leu-Phe-Phe-Val-Cys-Leu-Thr-Phe-Ser-{circumflex over ( )}
----------
Name: Sx6.8
Species: striolatus
Isolated: No
Cloned: Yes
DNA Sequence:
ATGAAACTGACGTGTATGGTGATCGTCGCCGTGCTGCTCCTGACGACCTGTCATCTC (SEQ ID NO:407)
ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGGTCGACTAC
CAAAGTCTCCAAGTCGACTAGCTGCATGAAAGCCGGGTCTTATTGCGTCGCTACTAC
GAGAATCTGCTGCGGTTATTGCGCTTATTTCGGCAAAATATGTATTGGCTATCCCAA
AAACTGATCCTCCCCCTACTGTGCTCTATCCTTTTCTGCCTGATGTCTTCTCCTCCCC
TC
Translation:
MKLTCMVIVAVLLLTTCHLITADDSRGTQKHRSLRSTTKVSKSTSCMKAGSYCVATTRI (SEQ ID NO:408)
CCGYCAYFGKICIGYPKN
Toxin Sequence:
Ser-Thr-Ser-Cys-Met-Lys-Ala-Gly-Ser-Xaa5-Cys-Val-Ala-Thr-Thr-Arg-Ile-Cys-Cys-Gly-Xaa5- (SEQ ID NO:409)
Cys-Ala-Xaa5-Phe-Gly-Lys-Ile-Cys-Ile-Gly-Xaa5-Xaa3-Lys-Asn-{circumflex over ( )}
Xaa1 is Glu or γ-carboxy-Glu
Xaa2 is Gln or pyro-Glu
Xaa3 is Pro or hydroxy-Pro
Xaa4 is Trp or bromo-Trp
Xaa5 is Tyr, 125I-Tyr mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr
Xaa6 is Nle
{circumflex over ( )} is free carboxyl or amidated C-terminus, preferably free carboxyl
# is free carboxyl or amidated C-terminus, preferably amidated
TABLE 2
Alignment of Conotoxin Peptide Sequences
δ-GmVIA [F15Y] -VKPCRKEGQLCDPIYQN---CCRGWNC--VLF-CV{circumflex over ( )} (SEQ ID NO:4)
δ-GmVIA [F27Y] -VKPCRKEGQLCDPIFQN---CCRGWNC--VLY-CV{circumflex over ( )} (SEQ ID NO:5)
Omaria9 M---CRREAQLCDPIFQN---CCHGLFC--VLV-CV{circumflex over ( )} (SEQ ID NO:8)
Tx6.11 QVKPCRKEHQLCDLIFQN---CCRGWYC--VVLSCT{circumflex over ( )} (SEQ ID NO:11)
Om6.6 ----CVPHEGPCNWLTQN---CCSGYNC--IIFFCL{circumflex over ( )} (SEQ ID NO:14)
Da6.2 QVKPCRKEHQLCDLIFQN---CCRGWYC--LLRPCI{circumflex over ( )} (SEQ ID NO:17)
Da6.6 -VKPCSEEGQLCDPLSQN---CCRGWHC--VLVSCV{circumflex over ( )} (SEQ ID NO:22)
δ-TxVIA [M8J] W---CKQSGEXCNLLDQN---CCDGY-C--IVLVCT{circumflex over ( )} (SEQ ID NO:24)
Da6.4 ----CLGGGEVCDIFFPQ---CC-GY-C--UVKVCT{circumflex over ( )} (SEQ ID NO:37)
Gm6.5 ----CRLGAESCDVISQN---CCQGT-C--VFF-CLP{circumflex over ( )} (SEQ ID NO:40)
Gm6.6 ----CKQADESCNVFSLD---CCTGL-C--LGF-CVS{circumflex over ( )} (SEQ ID NO:43)
Gm6.3 ----CVPYEGPCNWLTQN---CCDEL-C--VFF-CL{circumflex over ( )} (SEQ ID NO:46)
M6.5 ----CKQADEPCDVFSLE---CCTGI-C--LGF-CTW{circumflex over ( )} (SEQ ID NO:49)
Tx6.2 ----CLDAGEVCDIFFPT---CC-GY-C--ILLFCA{circumflex over ( )} (SEQ ID NO:52)
Om6.1 ----CLAEHETCNIFTQN---CCEGV-C--IFI-CVQAPE{circumflex over ( )} (SEQ ID NO:57)
Om6.3 ----CIPHFDPCDPIRHT---CCFGL-C--LLIACI{circumflex over ( )} (SEQ ID NO:60)
Om6.4 ----CLGFGEACLILYSD---CC-GY-C--VGAICL{circumflex over ( )} (SEQ ID NO:63)
Au6.1 ----CKAENELCNIFIQN---CCDGT-C--LLI-CIQNPQ{circumflex over ( )} (SEQ ID NO:66)
Au6.2 ----CLEFGELCNFFFPT---CC-GY-C--VLLVCM{circumflex over ( )} (SEQ ID NO:69)
Da6.5 ----CAQSSELCDALDSD---CCSGV-C--MVFFCD{circumflex over ( )} (SEQ ID NO:72)
Di6.4 ----CLGFGEACLMLYSD---CC-SY-C--VGAVCL{circumflex over ( )} (SEQ ID NO:75)
Pn6.2 ----CVKYLDPCDMLRHT---CCFGL-C--VLIACI{circumflex over ( )} (SEQ ID NO:78)
Pn6.3 ----CLGFGEVCNFFFPN---CC-SY-C--VALVCV{circumflex over ( )} (SEQ ID NO:81)
Pn6.4 ----CIPQFDPCDMVRHT---CCKGL-C--VLIACSKTA{circumflex over ( )} (SEQ ID NO:84)
Pn6.7 ----CKAESEACNIITQN---CCDGK-C--LFF-CIQIPE{circumflex over ( )} (SEQ ID NO:87)
Omaria3 ----CIDGGEICDIFFPN---CCSGW-C--IILVCA{circumflex over ( )} (SEQ ID NO:90)
Omaria1 ----CLDGGEICGILFPS---CCSGW-C--IVLVCA{circumflex over ( )} (SEQ ID NO:93)
Marm7 ----CLEFGEVCNFFFPT---CC-GY-C--VLLVCL{circumflex over ( )} (SEQ ID NO:96)
Marm12 ----CQEFGEVCNFFFPD---CC-GY-C--VLLLCI{circumflex over ( )} (SEQ ID NO:99)
Omaria7 ----CIPHFDPCDPIRHT---CCFGL-C--LLIACI{circumflex over ( )} (SEQ ID NO:102)
Omaria11 ----CLEFGEVCNFFFPT---CC-GY-C--VLLVCL{circumflex over ( )} (SEQ ID NO:105)
O6.5 SKKQCRQNGEVCDANLAH---CCSGP-C--FLF-CLNQP{circumflex over ( )} (SEQ ID NO:108)
Af6.8 ----CTQSGELCDVIDPD---CCNNF-C--IIFFCI{circumflex over ( )} (SEQ ID NO:111)
KK-2A ----CAPFLHLCTFFFPN---CCNGY-C--VQFICL{circumflex over ( )} (SEQ ID NO:114)
KKM1 ----CLDAGEMCDLFNSK---CCSGW-C--IILFCA{circumflex over ( )} (SEQ ID NO:117)
KKM4 ----CLDGGEICGILFPS---CCSGW-C--IVLVCA{circumflex over ( )} (SEQ ID NO:120)
KKM5 ----CPNTGELCDVVEQN---CCYTY-C--FIVVCPI{circumflex over ( )} (SEQ ID NO:123)
KKM6 -DDECEPPGDFCGFFKIGP-PCCSGW-C--PLW-CA{circumflex over ( )} (SEQ ID NO:126)
C. striatus S2 -DDECEPPGDFCGFFKIGP-PCCSGW-C--FLW-CA{circumflex over ( )} (SEQ ID NO:129)
Om6.5 -DDDCEPPGNFCGMIKIGP-PCCSGW-C--FFA-CA{circumflex over ( )} (SEQ ID NO:132)
Au6.3 -DYDCEPPGNFCGMIKIGP-PCCSGW-C--FFA-CA{circumflex over ( )} (SEQ ID NO:135)
Marm9 -DDDCEPPGNFCGMIKIGP-PCCSGW-C--FFA-CA{circumflex over ( )} (SEQ ID NO:138)
Rg6.4 -D--CLSKNAFCAWPILGP-LCCSGW-C--LYV-CM{circumflex over ( )} (SEQ ID NO:141)
R6.5 -GDDCLAVKKNCGFPKLGG-PCCSGL-C--FFV-CA{circumflex over ( )} (SEQ ID NO:144)
Rg6.2 D--CLPRDTFCALPQLGL-LCCSGR-C--LLF-CW{circumflex over ( )} (SEQ ID NO:147)
A6.5 -DG-CSNAGAFCG---IHPGLCCSEI-C--IVW-CT{circumflex over ( )} (SEQ ID NO:150)
δ-PVIA [F9A] -EA-CYAOGTACG---IKOGLCCSEF-C--LPGVCFG{circumflex over ( )} (SEQ ID NO:154)
δ-PVIA [I12A] -EA-CYAOGTFCG---AKOGLCCSEF-C--LPGVCFG{circumflex over ( )} (SEQ ID NO:155)
δ-PVIA [T8A] -EA-CYAOGAFCG---IKOGLCCSEF-C--FLW-CITFVDS# (SEQ ID NO:156)
M6.3 -DG-CYNAGTFCG---IRPGLCCSEF-C--FLW-CITFVDS#(SEQ ID NO:159)
M6.6 -DE-CYPPGTFCG---IKPGLCCSAI-C--LSFVCISF-DF{circumflex over ( )} (SEQ ID NO:162)
M6.7 -EA-CYNAGSFCG---IHPGLCCSEF-C--ILW-CITFVDS# (SEQ ID NO:165)
M6.8 -EA-CYNAGTFCG---IKPGLCCSAI-C--LSFVCISF-DF{circumflex over ( )} (SEQ ID NO:168)
E6.4 -EA-CYPPGTFCG---IKPGLCCSEL-C--LPAVCVG# (SEQ ID NO:171)
P6.4 -EA-CYPPGTFCG---IKPGLCCSEL-C--LPAVCVG# (SEQ ID NO:174)
δ-SVIE [D1E] -EG-CSSGGTFCG---IHOGLCCSEF-C--FLW-CITFID{circumflex over ( )} (SEQ ID NO:177)
δ-SVIE -DG-CSSGGTFCG---IHOGLCCSEF-C--FLW-CITFID{circumflex over ( )} (SEQ ID NO:180)
C6.2 -YG-CSNAGAFCG---IHPGLCCSEL-C--LVW-CT{circumflex over ( )} (SEQ ID NO:184)
C6.3 -YG-CSNAGAFCG---IHPGLCCSEL-C--LGW-CT{circumflex over ( )} (SEQ ID NO:187)
Di6.3 -YE-CYLLVHFCG---INGGLCCSNL-C--LFFVCLTFS{circumflex over ( )} (SEQ ID NO:190)
Rg6.1 -D--CLPDYTICA---FNMGLCCSDK-C--MLV-CLP{circumflex over ( )} (SEQ ID NO:193)
Rg6.3 -II-CFPDYMFCG---VNVFLCCSGN-C--LLI-CVP{circumflex over ( )} (SEQ ID NO:196)
Gm6.2 ----CYDGGTGCD----SGNQCCSGW-C--IFA-CL{circumflex over ( )} (SEQ ID NO:199)
Da6.1 ----CYDGGTGCD----SGNQCCSGW-C--IFV-CL{circumflex over ( )} (SEQ ID NO:202)
Pn6.6 ----CFESWVACE----SPKRCCSHV-C--LFV-CT{circumflex over ( )} (SEQ ID NO:205)
Di6.5 ----CNEAQEHCT----QNPDCCSES-CNKFVGRCLS--D{circumflex over ( )} (SEQ ID NO:208)
Af6.10 ----CYDGGTSCN----TGNQCCSGW-C--IFL-CL{circumflex over ( )} (SEQ ID NO:211)
Tx6.10 ----CYDSGTSCN----TGNQCCSGW-C--IFVSCL{circumflex over ( )} (SEQ ID NO:214)
Gm6.4 -D--CQALWDYCPVPLLSSGDCCYGLIC--GPFVCIGW{circumflex over ( )} (SEQ ID NO:217)
Gm6.2 KT--CQRRWDFCPGSLVGVITCCGGLIC--FLFFCV{circumflex over ( )} (SEQ ID NO:220)
Da6.3 -D--CQEKWDYCPVPFLGSRYCCDGFIC--PSFFCA{circumflex over ( )} (SEQ ID NO:223)
Da6.7 -D--CQGEWEFCIVPVLGFVYCCPWLIC--GPFVCVDI{circumflex over ( )} (SEQ ID NO:226)
Pn6.5 -G--CLEVDYFCGIPFVNNGLCCSGN-C--VFV-C--TPQ# (SEQ ID NO:229)
Marm6 ----CLNVDYFCGIPFVNNGLCCSGN-C--VFV-C--TPQ# (SEQ ID NO:232)
Marm15 -E--CLEADYYCVLPFVGNGMCCSGI-C--VFV-CIAQRFKTV{circumflex over ( )} (SEQ ID NO:235)
Marm10 -D--CLEPDYVCGIPFVFNGLCCSGI-C--VFI-CIAQKY{circumflex over ( )} (SEQ ID NO: 238)
Marm14 -A--CSKKWEYCIVPILGFVYCCPGLIC--GPFVCV{circumflex over ( )} (SEQ ID NO:241)
Omaria14 -D--CLNVDYFCGIPFVNNGLCCSGN-C-VF--CLHTPREVKLP{circumflex over ( )} (SEQ ID NO:244)
O6.4 ----CLVYGTPCDWLTIAGMECCSKK-C--FMM-CW{circumflex over ( )} (SEQ ID NO:247)
R6.4 -D--CHEVGEPCGLPLIKNGLCCSQI-C--LGV-CAKVF{circumflex over ( )} (SEQ ID NO:250)
R6.6 -E--CTANGEFCGISVFGSYLCCSGR-C--VFV-CI{circumflex over ( )} (SEQ ID NO:253)
R6.7 -E--CTTNGEFCGISVFASFLCCSGL-C--VFV-CI{circumflex over ( )} (SEQ ID NO:256)
R6.8 -K--CPPKNHPCGFVVMLNYLCCSGR-C--IFV-CV{circumflex over ( )} (SEQ ID NO:259)
Rg6.5 -S--CLPLDWFCGFNIIGAFLCCSGY-C--LVV-CW{circumflex over ( )} (SEQ ID NO:262)
De6.2 -D--CIPGGENC--DVFRPYRCCSGY-C--ILLLCA{circumflex over ( )} (SEQ ID NO:265)
Striat21 -LRWCIPSGELC--FRSDHIGCCSGK-C--AFV-CL{circumflex over ( )} (SEQ ID NO:268)
δStriatus 26 ---WCIPSGDLC--PRSDHIGCCSGK-C--AFV-CL{circumflex over ( )} (SEQ ID NO:271)
δStriatus 106 ---WCIPSGDLC--FRSDHIQCCSGK-C--AFV-CM{circumflex over ( )} (SEQ ID NO:274)
O6.3 -LRWCVPSGEVC--RRYEPVGCCSGK-C--FFV-CS{circumflex over ( )} (SEQ ID NO:277)
R6.3 ----CLPDGTSC---LFSRIRCC-GT-CSSILKSCVS{circumflex over ( )} (SEQ ID NO:280)
Ak6.1 (F763) ----CRPRGMFCGFPKPGPY-CCNGW-CF--FV-CI{circumflex over ( )} (SEQ ID NO:328)
Ar6.11 (G21) ----CLEKCVLCD--PSAGN-CCSGE-CV--LV-CL{circumflex over ( )} (SEQ ID NO:307)
Ar6.12 (G20) -E--CVAGSHFCGFPKIGGP-CCSGW-CP--FV-CM{circumflex over ( )} (SEQ ID NO:310)
Ar6.5 (F008) -D--CRPVGQYCGIPYKHNWRCCSQL-CA--II-CVS{circumflex over ( )} (SEQ ID NO:304)
Ca6.5 (G211) ----CVDPGEPCG--PGPGD-CCTGP-CL--LV-CI{circumflex over ( )} (SEQ ID NO:322)
Ep6.1 (J425) ----CLGPGEACL--MLYSD-CCS-Y-CV-ALV-CL{circumflex over ( )} (SEQ ID NO:340)
Ep6.2 (J424) -G--CLAVDYPCGIPFVSNGLCCSGN-CV--FV-CTPQ# (SEQ ID NO:343)
G6.3 -DDECEPPGDPCGPPKIGPP-CCSGW-CP--LW-CA{circumflex over ( )} (SEQ ID NO:283)
Ge6.1 (G18) -G--CLDPGYPCGTPFLCAY-CCGGI-CL--IV-CIET{circumflex over ( )} (SEQ ID NO:337)
Im6.1 (F076) Q---CRVEGEICGML-FEAQ-CCDGW-CP--FV-CW{circumflex over ( )} (SEQ ID NO:319)
Lp6.5 (A667) -A--CVELCEICATGFFLDEECCTGS-CH--VF-CVM{circumflex over ( )} (SEQ ID NO:292)
Lv6.1 (F775) ----CPNTGELCDV--VEQN-CCYTY-CF-IVV-CM{circumflex over ( )} (SEQ ID NO:331)
Mf6.2 (G218) ----CLPNGVLCDL--GSPPYCCSGW-CA-IVV-CI{circumflex over ( )} (SEQ ID NO:325)
Mr6.4 (A666) ----CPNTCELCDV--VEQN-CCYTY-CF-IVV-CL{circumflex over ( )} (SEQ ID NO:295)
Pu6.3 (F770) ----CVEDGDFCG--PGYEE-CCSCP-CL--YV-CI{circumflex over ( )} (SEQ ID NO:334)
Qc6.1 ----CAAAGEACVIPIIGNVPCCKGY-CL--FV-CIS{circumflex over ( )} (SEQ ID NO:289)
Qc6.2 (F024) -DGDCVDGGEPCGPPKIGGP-CCSGW-CP--FV-CL{circumflex over ( )} (SEQ ID NO:298)
Qc6.3 (F026) -D--CQDSGVVCGPPKPEPH-CCSGW-CL--FV-CA{circumflex over ( )} (SEQ ID NO:301)
Ts6.2 (F078) -D--CWPQYWFCGLQRG----CCPGTTCF--FL-CF{circumflex over ( )} (SEQ ID NO:313)
Ts6.4 (F080) ---WCALDGELCIIPVIGSIFCCHGI-CM--IY-CV{circumflex over ( )} (SEQ ID NO:316)
Tx6.8 ----CYDSGTSC---NTGNQ-CCSGW-CI--FV-CL{circumflex over ( )} (SEQ ID NO:286)
Ac6.1 W---CIPRGDLC-FPSDRIQ-CCSGK-CTF---VCM{circumflex over ( )} (SEQ ID NO:346)
Ac6.2 -G--CVPSGEIC-YPMDHIC-CCSGK-CTF---VCM{circumflex over ( )} (SEQ ID NO:349)
Bu6.7 -DE-CSAPGAPCL--IRPGL-CCSEP-C-FF--ACE{circumflex over ( )} (SEQ ID NO:352)
Bu6.8 -G--CLPRWEPC-PIPKKND-CCSGI-CIS---ICM{circumflex over ( )} (SEQ ID NO:355)
Cn6.10 -DG-CYNAGTPCG--IRPGL-CCSEP-C-FL--WCITFVDS# (SEQ ID NO:364)
Cn6.9 -YE-CYSTGTFCG--INGGL-CCSNL-CLFF--VCLTFS{circumflex over ( )} (SEQ ID NO:361)
Cr6.5 W---CIPSGDLC-FPSDHIQ-CCSAK-CAF---VCL{circumflex over ( )} (SEQ ID NO:370)
Cr6.5A ----CIPSGDLC-FPSDHIQ-CCSAK-CAF---VCL{circumflex over ( )} (SEQ ID NO:373)
Cr6.6 ----CIPSGDLC-FPSDHIQ-CCNAK-CAF---VCL{circumflex over ( )} (SEQ ID NO:367)
Cr6.6A ----CIPSGDLC-FPSDHIQ-CCNAE-CAF---VCL{circumflex over ( )} (SEQ ID NO:376)
Cr6.5B W---CIPSGDLC-FPSDHIR-CCSAK-CAF---VCL{circumflex over ( )} (SEQ ID NO:379)
Cr6.6B ----CIPSGDLC-FPSDHIQ-CCNAK-CAF---ACL{circumflex over ( )} (SEQ ID NO:382)
Cr6.6C W---CIPSGDLC-FPSDHIQ-CCNAK-CAF---VCM{circumflex over ( )} (SEQ ID NO:285)
Cr6.7 W---CIPTGDLC-PPSDHIQ-CCSCK-CTF---VCM{circumflex over ( )} (SEQ ID NO:388)
Mn6.3 -YE-CYSTGTFCG--INGGL-CCSNL-CLFF--VCLTFS{circumflex over ( )} (SEQ ID NO:391)
Sm6.5 W---CIPSGELC-FRSDHIQ-CCSAK-CAF---VCL{circumflex over ( )} (SEQ ID NO:394)
Sm6.6 -DC-CSSGGTFCG--IRPGL-CCSEF-C-FL--WCITFID{circumflex over ( )} (SEQ ID NO:397)
Sx6.4 -D--CLAKDAFCAWPILGPL-CCSRL-CLY---VCM{circumflex over ( )} (SEQ ID NO:358)
Sx6.5 ----CRPGGTVCGFPKPGPY-CCSGW-CFF---VCA (SEQ ID NO:400)
Sx6.6 -EA-CYPPGTPCG--IKPGL-CCSEL-CLPA--VCVG# (SEQ ID NO:403)
Sx6.7 -YE-CYSTGTPCG--INGGL-CCSNL-CLPP--VCLTFS{circumflex over ( )} (SEQ ID NO:406)
Sx6.8 STS-CMKAGSYCVATTR--I-CC-GY-CAYPGKICIGYPKN{circumflex over ( )} (SEQ ID NO:409)
X is Nle
It will be appreciated that the methods and compositions of the instant invention can be incorporated in the form of a variety of embodiments, only a few of which are disclosed herein. It will be apparent to the artisan that other embodiments exist and do not depart from the spirit of the invention. Thus, the described embodiments are illustrative and should not be construed as restrictive.
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