Abstract: The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an -SMe group; (b) allowing the -SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

Abstract: The invention relates to small cell penetrating peptides (CPP) derived from the scorpion toxin maurocalcine and to their use as vectors for the intracellular delivery of various drugs and agents.

Abstract: It is an object of the present invention to provide a method for producing an 11-sugar sialylglycopeptide easily and with good yield and a high degree of purity on an industrial scale from defatted bird egg yolks. The present invention provides a production method of an 11-sugar sialylglycopeptide. More specifically, the present invention provides a production method of an 11-sugar sialylglycopeptide comprising: an extraction step of extracting defatted bird egg yolks with water or a salt solution to obtain a liquid extract of a glycopeptide, a precipitation step of adding the liquid extract to a water-soluble organic solvent to precipitate the glycopeptide, and a desalting step of desalting the precipitate.

Abstract: A delivery system is described that includes a polymer network that can incorporate a therapeutic peptide for targeted delivery to a cell, e.g., a cancer cell. The polymer network can secure the therapeutic peptide via two different mechanisms. First, a polymer of the network can interact with the therapeutic peptide via charge/charge interaction to form a complex with the peptide, thereby holding the peptide within the network. Second, the polymer network can be crosslinked, providing another level of securement for holding the therapeutic peptide within the network. The two levels of securement can be reversible, and following delivery of the network to the interior of a targeted cell reversal of the securement mechanisms can release the therapeutic peptide within the cell.

Abstract: The présent invention relates to cell-penetrating peptides characterized in that it comprises an amino acid séquence selected in the group consisting of X1LX2RALWX9LX3X9X4LWX9LX5X6X7X8, X1LX2LARWX9LX3X9X4LWX9LX5X6X7X8 and X1LX2ARLWX9LX3X9X4LWX9LX5X6X7X8, wherein X1 is beta-A or S, X2 is F or W, X3 is L, W, C or I, X4 is S, A, N or T, Xs is L or W, X6 is W or R, X7 is K or R, X8 is A or none, and X9 is R or S. Thèse peptides exhibit high efficiency, low toxicity and a natural tropism for lung tissues, and can be used either in simple complex with the cargo to be vectorised, or in nanoparticles comprising two layers of cell-pentrating peptides around the cargo.

Abstract: The present invention provides parathyroid hormone and/or parathyroid hormone-related protein analogs, compositions thereof and methods thereto.

Abstract: The invention relates to isolated DNA or RNA molecules comprising at least ten contiguous bases having a sequence in a pancreatic islet microRNA. In another embodiment, the invention relates to isolated single stranded pancreatic islet microRNA molecules or anti-pancreatic islet microRNA molecules.

Abstract: Provided herein are compositions and kits comprising a therapeutic agent linked to a cleavable substrate, wherein the cleavable substrate is capable of being cleaved by cathepsin E. Also provided are methods of treating one or more symptoms of a disease or disorder characterized by expression of cathepsin E in a subject and methods of eliminating a cancer cell characterized by expression of cathepsin E using the provided compositions and kits. Further provided herein are methods of detecting the presence of a cancer cell or detecting a cathepsin E expressing cell using a photosensitizer linked to a cleavable substrate, wherein the cleavable substrate is capable of being cleaved by cathepsin E.

Abstract: The invention provides a conjugate of a biologically active molecule and a 5-fluoro-5-deoxypentose or a 3-fluoro-3-deoxypentose, wherein the biologically active molecule is selected from the group consisting of proteins, peptides, nucleic acids, oligosaccharides and polysaccharides.

Abstract: The disclosure provides cationic peptidopolysaccharides of Formula I: which has a bacterial peptidoglycan-mimetic structure, and shows outstanding broad spectrum activities against clinically significant bacteria and fungi. The structural affinity of these compounds with microbial cell wall constituents promotes its passage to the cytoplasmic membrane resulting in excellent antimicrobial activity and record high selectivity.

Abstract: Antimicrobial compositions including a cell penetrating peptide (CPP) having the amino acid sequence Tyr-Ala-Arg-Val-Arg-Arg-Arg-Gly-Pro-Arg-Gly-Tyr-Ala-Arg-Val-Arg-Arg-Arg-Gly-Pro-Arg-Arg (SEQ ID NO:1) or variant thereof are disclosed. The CPP, which itself has antimicrobial properties, can be advantageously combined with or conjugated to a cargo to increase the delivery, efficacy, or combinations thereof, of the cargo into cells. In preferred embodiments, the CPP is combined with or conjugated to a functional nucleic acid, such as an external guide sequence (EGS) which can target and reduce expression of essential microbial genes or genes than impart resistance to antimicrobial drugs. Methods of using the compositions alone or in combination with traditional antimicrobial drugs to treat infections are also disclosed.

Abstract: Novel methods of native chemical ligation are provided. The methods involve reacting a thioacid (e.g. a peptide thioacid) with an aziridinyl compound (e.g. an aziridinyl peptide) or glycosylamine under mild conditions without the use of protecting groups, and without requiring that a cysteine residue be present in the ligation product. Initial coupling of the thioacid and the aziridinyl compound yields a ligation product containing an aziridinyl ring. Optional subsequent opening of the aziridinyl ring (e.g. via a nucleophilic attack) produces a linearized and modified ligation product. Coupling of a peptide thioacid and glycosylamine yields a glycosylated peptide.

Abstract: A glycolipopeptide comprising a carbohydrate component, a peptide component and a lipid component, for use as a therapeutic or prophylactic vaccine. Also provided are monoclonal and polyclonal antibodies that recognize the glycolipopeptide of the invention, as well as uses thereof.

Abstract: Described herein are CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, compositions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic peptide conjugates, and kits comprising CDP-therapeutic peptide conjugates. Also disclosed are methods of using (e.g., to treat a disorder) the CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, compositions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic peptide conjugates, and kits comprising CDP-therapeutic peptide conjugates.

Abstract: Disclosed are RNA targeting compounds, methods for using the subject RNA targeting compounds to treat myotonic dystrophy and other diseases are also disclosed.

Abstract: The invention relates to kisspeptide-pentasaccharide conjugates having the general formula (I) wherein Z1 is Tyr or D-Tyr; Z3 is Trp, Hyp, Phe or Lys(R2); Z5 is Thr, Aib or Ala; Z7 is Gly or azaGly; Z8 is Leu; or Z7 and Z8 together represent; Z10 is Phe or Trp; n is 0 or 1; or R2, when present, represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SO3X; X is a positively charged counterion; with the proviso that when R2 is present, R1 is H or (C1-6) alkylcarbonyl; R3 is H or (C1-3)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same as well as to the use of said kisspeptide-pentasaccharide conjugates in the treatment of female infertility.

Abstract: Reagents and methods for functionalizing polypeptides with moieties poly (alkylene glycol) molecules and glycan groups are disclosed that are based on a functionalizing reagent which comprises a nitrogen containing heterocyclic aromatic ring having a vinyl substituent that is capable of reacting with one or more thiol groups that are naturally present, or have been introduced into, the polypeptide, for example by employing a thiol group of one or more cysteine residues. The functionalizing reagent is covalently linked to a poly (alkylene glycol) molecule, such as a polyethylene glycol (PEG) molecule, or a glycan group so that the reaction between the vinyl group and the thiol group in the polypeptide covalently links the polypeptide to the poly (alkylene glycol) molecule and/or the glycan group.

Abstract: In one aspect, the invention relates to isolated compounds useful as antifungal agents, for example, compounds having a structure represented by a formula: wherein R1 is hydrogen or hydroxyl; wherein R2 is hydrogen or xylose; and wherein R3 and R4 are each hydrogen or together oxygen, or a pharmaceutically acceptable salt thereof; methods of isolating and purifying same; pharmaceutical compositions comprising same; agricultural compositions comprising same; and methods of treating and/or preventing fungal infections using same. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present application discloses novel glycoproteins and a related glycosylcarbamoylation methodology suitable for the preparation of glycopeptides (in particular glycoproteins and glycosylated cells), as well as the use of such glycoproteins in medicine, e.g. as pharmaceuticals and diagnostics or in diagnostic kits. A method for the preparation of a carbohydrate-peptide conjugate includes reacting a cyclic carbamate with a peptide which has at least one primary amino group.

Abstract: Novel glycopeptide antibiotic derivatives. These derivatives are represented by the formula (aglycon part of glycopeptide antibiotic derivative)-(Sac-NH)—RA [wherein (aglycon part of glycopeptide antibiotic derivative) is the part formed by removing the sugar part from a known glycopeptide antibiotic derivative; (Sac-NH) part is an amino sugar part or a sugar chain part containing an amino sugar; and RA represents, e.g., the formula —X1—Ar1—X2—Y—X3—Ar2 (wherein X1, X2, and X3 each represents 1) a single bond or 2) a heteroatom or heteroatom-containing group selected from the group consisting of —N?, ?N—, —NR1—, —O—, etc.; Y represents —NR2CO— or —CONR2— (wherein R2 represents hydrogen or lower alkyl), etc.)]. These derivatives have antibacterial activity against vancomycin-resistant bacteria.

Abstract: The invention provides a delivery system comprising a cell penetrating peptide, 10 histidines, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.

Abstract: To develop glucosamine (GlcN) pro-drugs with properties superior to the presently available GlcN products, we have synthesized derivatives with improved pharmaceutical properties. The synthesized derivatives include peptide-GlcN ester and amide conjugates where the peptide portion consists of one or more amino acids. One such compound is (5-amino-3,4,6-trihydroxyoxan-2-yl)methyl 2-(2-aminoacetamido)-3-methylbutanoate or glycine-valine-COO-GlcN (GV-GlcN).7.

Abstract: The invention relates, in part, to compositions and methods that utilize a peptide tag that binds to hemagglutanin (HA). The HA tag can be linked to a molecule such as a protein or nucleic acid which, when administered to the eye, results in an increase in ocular half-life and/or mean residence time, and or a decrease in ocular clearance of the protein or nucleic acid. The invention also encompasses methods for treating ocular disease, including retinal vascular disease, by administering a protein or nucleic acid linked to an HA peptide tag.

Abstract: The present invention relates to reagents and methods for purifying pertussis toxin (PT).

Abstract: The present invention discloses novel macromolecule transduction domain (MTD) peptides which facilitate the traverse of a biologically active molecule across the cell membrane. Also disclosed are polynucleotides encoding the MTD peptides, methods of identifying the MTD peptides; methods of genetically engineering a biologically active molecule to have cell permeability by using the MTD peptides, methods of importing a biologically active molecule into a cell by using the MTD peptides, and uses thereof.

Abstract: The present invention relates to compounds, and pharmaceutically acceptable salts thereof, comprising a vascular disrupting agent (VDA) associated and a MMP proteolytic cleavage site. The compounds are useful in the treatment of cancer.

Abstract: Transport peptides, alone or attached to a cargo moiety, are capable of targeted axonal import into the spinal cord and other structures of the central nervous system. The transport peptides can be used to deliver therapeutic agents and other molecules of interest from the periphery to the central nervous system, providing a means to detect, treat or prevent neurodegenerative diseases, stroke, chronic pain and other conditions via minimally invasive techniques of administration.

Abstract: The subject-matter of the present invention are nanocomplexes of polyanions and cationic peptides which are, e.g., suitable for the transport of drugs into cells and their controlled release in the organism, as well as a complex material in which the nanocomplexes are bonded to a biologically active unit for the selective recognition of tissues, cells or organelles.

Abstract: The present invention relates to a method for preparing carbohydrate T cell epitope conjugates of formula (I): M(T-B)n(I) wherein M, T, B and n are as defined in claim 1.

Abstract: An isolated or purified compound is provided, comprising A-GlcNAc[GlcNAc]-GalNAc-GalNAc-QuiNAc4NAc, wherein A is GlcNAc or Glc. There is further provided a vaccine based on such compound, having particular use to treat or prevent an infection caused by a Campylobacter organism. There is also provided an antibody or antisera against the compound, having particular use to diagnose the presence of an infection caused by a Campylobacter organism.

Abstract: The present disclosure provides modified bacteria and modified peptidoglycan comprising modified D-amino acids; compositions comprising the modified bacteria or peptidoglycan; and methods of using the modified bacteria or peptidoglycan. The modified D-amino acids include a bioorthogonal functional group such as an azide, an alkyne or a norbornene group. Also provided are modified peptidoglycans conjugated to a molecule of interest via a linker.

Abstract: The present invention relates to a macromolecule comprising a dendrimer having surface amino groups to which at least two different terminal groups are attached including a pharmaceutically active agent and a pharmacokinetic modifying agent, the pharmaceutically active agent comprising a hydroxyl group and being attached to the surface amino group of the dendrimer through a diacid linker. Pharmaceutical compositions comprising the macromolecules and methods of treatment using the macromolecules are also described.

Abstract: The invention features vancomycin class compounds modified to be suitable for oral delivery or to possess increased antimicrobial potency, formulations for the oral administration of vancomycin class compounds, and synthetic methods for making vancomycin class compounds.

Abstract: Compositions and methods are provided including a transporter peptide derived from the loop2 domain of the neuronally-derived lynx1 protein which can be conjugated to an effector agent to form a transporter-effector complex for transport of the therapeutic effector agent to a target that is found across the blood brain barrier.

Abstract: The invention relates to a method for the sequence information of PNA molecules of a specific PNA molecule species, wherein, the PNA molecules are contacted with different nucleic acid molecule species comprising nucleic acid molecules with nucleotides, wherein the nucleic acid molecules partially comprise a nucleic acid sequence that is complementary to a partial sequence of the PNA molecule, wherein nucleic acid molecules having complementary sequences bind to the PNA molecules forming nucleic acid/PNA hybrids, wherein nucleic acid molecules with non-complementary sequences are separated from the hybrids, wherein thereafter the hybrids are dissociated into single stranded hybrid nucleic acid molecules and PNA molecules, wherein the single stranded hybrid nucleic acid molecules are subjected to a sequencing process providing hybrid sequence information about the single stranded hybrid nucleic acid sequence, and wherein the hybrid sequence information is optionally translated into the complementary PNA sequen

Abstract: A conjugate molecule comprising an oligo- or polysaccharide covalently bound to a carrier and its use as potential vaccine against infection by S. Flexneri.

Abstract: Templated conjugates created from naturally-occurring protein sequences found in pathogens, such as viruses, are disclosed. The sequences are “templated” into a consensus coiled-coil sequence in a platform in order to form a two-stranded antigen suitable for immunization of a subject.

Abstract: The invention provides a compound of formula (I), wherein R1 is H, C(NH)NH2, an amino acid, or a peptide; X is OH, NH2, NHR2, NR2R3, an amino acid, or a peptide; R2 and R3 are selected from alkyl, alkylenearyl, or alkyleneheteroaryl; each R4 and R5 is independently H or CH3; Z is 2-amino-2,3-dihydro-1H-indene-2-carboxylic acid; 2-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid; 6-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene 6-carboxylic acid; cyclohexylalanine; cyclohexylglycine; homophenylalanine; 1-naphthylalanine; 2-naphthylalanine; 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; or octahydro-1H-indole-2-carboxylic acid; n is 0, 1, 2, 3, or 4; with the proviso that X is not NH2 when R1 is H, R4 is H, R5 is CH3, Z is Aci, and n is 2; or a pharmaceutically acceptable salt, ester or solvate thereof. A method of treating pain and a method for treating a mu-opioid receptor mediated disorder and/or a delta-opioid receptor mediated disorder also are provided.

Abstract: The present invention relates to a system for intracellular delivery of a cargo comprising at least one component A chosen from aliphatic linear or branched moieties with at least 4 carbon atoms and/or cyclic ring systems comprising 2-4 rings which may contain several hetero atoms chosen from N, S, O and P, wherein component(s) A is (are) attached to a cell penetrating peptide B and/or a non-peptide analogue thereof. It also relates to methods of using the system in diagnosis of diseases, as research tool and as a targeting system, a composition comprising the system and especially a pharmaceutical composition a material covered with the system and a material having the delivery systems into the material. Finally it relates to novel peptides.

Abstract: Derivatives of PSAs are synthesised, in which a reducing and/or non-reducing end terminal sialic acid unit is transformed into a N-hydroxysuccinimide (NHS) group. The derivatives may be reacted with substrates, for instance substrates containing amine or hydrazine groups, to form non-cross-linked/crosslinked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs, peptides or proteins or drug delivery systems.

Abstract: At least some embodiments of the invention relates to an implant having a coating that contains or is composed of a functionalized RGD peptidomimetic RGD-P1 having the formula (1) and/or a functionalized RGD peptidomimetic RGD-P2 having the formula (2), and an associated manufacturing method.

Abstract: The invention provides a delivery system comprising a cell penetrating peptide, a polyarginine peptide, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.

Abstract: The subject invention pertains to agonist peptides of type I interferons and methods of using the peptides. These peptides are based on the amino acid sequence of the C-terminus region of the type I IFN molecules and are capable of binding to the cytoplasmic domain of type I IFN receptors. Surprisingly, these peptides were found to possess the same or similar biological activity as that associated with the full-length, mature type I IFN proteins, even though these peptides do not bind to the extracellular domain of the type I IFN receptors. In one embodiment, the peptide is a peptide of IFN?. In another embodiment, the peptide is a peptide of IFN?. Exemplified peptides of the invention include those having SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:38, SEQ ID NO:39, and SEQ ID NO:40. The subject peptides have been shown to effect increased resistance to viral infection.

Abstract: The present invention provides methods for synthetic antibodies, methods for making synthetic antibodies, methods for identifying ligands, and related methods and reagents.

Abstract: The present disclosure provides inter alia conjugates of formula (I): wherein n, R1, R2, Rx, Z, X, Y and Z are as defined herein. A conjugate of formula (I) can also be converted to a conjugate of formulae (II) or (III) as described herein. Without limitation, the conjugates can be used to make controlled release materials and chemical sensors.

Abstract: The present invention generally relates to methods and compositions for generating vancomycin analogs. Specifically the invention relates to generating a vancomycin library through chemoselective ligation of a sugar moiety with a vancomycin aglycon. In particular, the present invention provides a library of vancomycin analogs, where the member of the library comprises at least one vancomycin analog selected from 2?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 3?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 4?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 6?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 2?-N-acylbiphenyl-glucosyl vancomycin neoglycoside, 3?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside, 4?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside and 6?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside.

Abstract: The present invention relates to novel complex peptidomimetic products comprising multiple homogeneous or heterogeneous pendant groups that are site-specifically positioned along a linear oligomer or polymer scaffold and methods of making thereof. More specifically, the invention relates to N-substituted glycine peptoid oligomers or peptoids and their use as substrates for azide-alkyne [3+2]-cycloaddition conjugation reactions and subsequent additional rounds of oligomerization and cycloaddition. The methods of the invention may also be used to generate peptoid-peptide hybrid or peptide products comprising multiple homogeneous or heterogeneous pendant groups, which are positioned precisely along the linear oligomer or polymer scaffold.

Abstract: This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: The invention relates to conjugates comprising a targeting moiety specific for the CXCR4 based on the polyphemusin-derived peptide and a therapeutic or imaging agent. The invention relates as well to the application of said conjugates for the therapy and diagnostics which require the specific targeting to CXCR4+ cells.