Abstract: A process for separating organic compounds from a mixture by reverse-phase displacement chromatography, including providing a hydrophobic stationary phase; applying to the hydrophobic stationary phase a mixture comprising organic compounds to be separated; displacing the organic compounds from the hydrophobic stationary phase by applying thereto an aqueous composition comprising a non-surface active hydrophobic neutral zwitterionic displacer molecule and optionally an organic solvent; and collecting a plurality of fractions eluted from the hydrophobic stationary phase containing the separated organic compounds; in which the non-surface active hydrophobic neutral zwitterionic displacer molecule comprises a hydrophobic zwitterion having the general formula, as defined in the disclosure: [CM-R*—CM?].

Abstract: Methods and materials are provided for the production of glycosylated peptides that exhibit high affinity and specificity for delta opioid receptors. The methods and materials of the present invention may be used for treatment of conditions involving pain, such as acute pain and nociceptic pain, neuralgia and myalgia.

Abstract: A toner for developing an electrostatic charge image which contains a polyester resin as a binder resin is provided. The toner has excellent toner properties including low temperature fixing properties, anti-blocking property and anti-offset property, etc. Also a polyester resin for a toner is provided, which is used in the above-mentioned toner. As the binder resin for toner, a polyester resin comprising (1) an aromatic dicarboxylic acid and (2) a disproportionated rosin as an acid component, and (3) a tri- or more-valent polyhydric alcohol as an alcohol component is used, wherein the molar ratio (3)/(1) of the alcohol component (3) and the acid component (1) is from 1.05 to 1.65 and the molar ratio (2)/(1) of the acid components (2) and (1) is from 0.40 to 2.60.

Abstract: Disclosed is a method of analyzing an oxidation state of a methionine residue in a protein sample, which comprises the steps of: inducing a reaction between a protein sample having a methionine residue with an oxidation state to be analyzed, and hydrogen peroxide H218O2 having oxygen atoms labeled by the isotope 18O, to obtain a modified protein sample in which the oxidation state of the methionine residue is stabilized; and subjecting the modified protein sample to a measurement to quantify an oxidation degree of the methionine residue. Preferably, the measurement is a mass spectrometric (MS) measurement using a mass spectrometer. The method can analyze an oxidation state of a methionine residue in a protein sample, in a simple manner, while accurately reflecting an in vivo oxidation state of the methionine residue.

Abstract: A compound provided by the present invention includes an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently bonded to a biologically active peptide. One example of an inventive compound described is a conjugate of an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently coupled to an opioid peptide, such as an endorphin, enkephalin, dynorphin or endomorphin. Also detailed are processes for making the described conjugates and pharmaceutical compositions including such compounds.

Abstract: Novel polypeptide derivatives having protracted profile of action.

Abstract: Compositions comprising a lipophilic derivative of a hydrophilic drug and an amphiphile compound for use in therapy of the human or animal body are provided. Methods of medical treatment, wherein a composition according to the invention is administered to a human or animal body also form part of the invention. It is preferred that the drug is delivered to the brain.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: Provided is a factor capable of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time. More particularly, provided are a method of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time by adding a compound derived from proopiomelanocortin (POMC) to an undifferentiated (nucleated) erythrocyte, and an enucleation inducer including the compound.

Abstract: The invention is directed to a pharmacologically active peptide conjugate having a reduced tendency towards enzymatic cleavage comprising a pharmacologically active peptide sequence (X) and a stabilising peptide sequence (Z) of 4-20 amino acid residues covalently bound to X.

Abstract: Amphipathic glycopeptides, the amino acid sequence of which comprises an N-terminal opioid message sequence, a C-terminal helical address sequence, and a linker sequence between the message sequence and the helical address sequence, where the C-terminal helical address sequence has a length of nine amino acids, and at least one of the amino acid residues of the peptide is glycosylated. The peptides are useful for relieving pain, providing analgesia and treating anxiety, depression, obesity, anorexia nervosa, phobias, schizophrenia, Parkinson's disease and Alzheimer's disease.

Abstract: Process for purifying a recombinant protein including one or a few procedural steps only. The process combines the step of lysis of the host cell, with the purification of the protein of interest, allowing for a rapid and much more efficient process of purification. The conditions used during the purification process are those of a high temperature and a low pH, allowing for thermostable and acid-resistant recombinant proteins to be isolated from a suspension. The invention also relates to purifying recombinant proteins which are fusion proteins, wherein one part of the protein may be selected from an enamel matrix protein, such as amelogenin.

Abstract: The present invention provides a method of synthesizing an intramolecularly bridged polypeptide comprising at least one intramolecular bridge. The present invention further provides a method of synthesizing an intramolecularly bridged polypeptide comprising two intramolecular bridges, wherein the two intramolecular bridges form two overlapping ring, two rings in series, or two embedded rings. The present invention also provides methods for synthesizing lantibiotics, including Nisin A. Additionally, the invention provides intramolecularly bridged polypeptides synthesized by the methods disclosed herein and differentially protected orthogonal lanthionines.

Abstract: Glycopeptides which are amphipathic and capable of crossing the blood-brain-barrier are provided. The glycopeptides are useful for treating a variety of neurological an behavioral disorders.

Abstract: A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.

Abstract: A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has at least two of the glycosylation sites proximal to the CD4 binding site or chemokine receptor site altered so that the alteration prevents glycosylation at that site or where glycosylation sites distal to these sites have been derivatized with a molecular adjuvant, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has both changes. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp 120.

Abstract: A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.

Abstract: Genetically-encodable, environmentally-responsive fusion proteins comprising ELP peptides. Such fusion proteins exhibit unique physico-chemical and functional properties that can be modulated as a function of solution environment. The invention also provides methods for purifying the FPs, which take advantage of these unique properties, including high-throughput purification methods that produce high yields (e.g., milligram levels) of purified proteins, thereby yielding sufficient purified product for multiple assays and analyses. The high throughput purification technique is simpler and less expensive than current commercial high throughput purification methods, since it requires only one transfer of purification intermediates to a new multiwell plate.

Abstract: The invention provides novel inclusion complexes of highly potent opioid peptide of L-Tyrosyl-D-alanyl-glycyl-N-methylphenylalanyl-glycyl-isopropylamide with cyclodextrin, pharmaceutical preparations containing these inclusion complexes of L-Tyrosyl-D-alanyl-glycyl-N-methylphenylalanyl-glycyl-isopropylamide with cyclodextrin derivatives, the complexes being better soluble in water and having improved biopharmaceutical properties such as lesser toxicity, better analgesic action and non-addiction properties.

Abstract: The present invention is related to the treatment and prevention of cancer including particularly gastrointestinal cancer. More specifically, the present invention describes the use of naltrexone, naloxone and the pentapeptide growth factor [Met5]-enkephalin to inhibit and arrest the growth of cancer. Such efficiency has been discovered to be a consequence of the functional manipulation of the zeta (&zgr;) opioid receptor through endogenous [Met5]-enkephalin. This receptor has been determined to be present in growing cancers such as pancreatic and colon cancer, for example.

Abstract: Disclosed are lanthionine bridged peptides having the structure methods of their preparation and their use as pharmacologically active agents.

Abstract: An active &bgr;-endorphin fragment or an analog of such a fragment is provided to a patient for alleviating the effect of muscle-wasting disease and for inhibiting or reducing leakage of an enzyme from a living muscle. The &bgr;-endorphin fragment is selected from &bgr;-endorphin (30, 31), &bgr;-endorphin (29-31), &bgr;-endorphin (28-31) and stabilized analogs thereof.

Abstract: The present invention relates to a pharmaceutical composition for the nasal transmucosal delivery of a biocompatible polymer-biologically active peptide conjugate. The pharmaceutical composition of the present invention increases the water solubility of peptide, which is sparingly soluble in water, improves its stability by protecting it from being degraded by proteases. As a result, the number of administrations of the drug and the side-effects induced by drug abuse are decreased. In addition, since the pharmaceutical composition of the present invention is delivered through the nasal cavity, it allows drug activity to be expressed in a short period of time and improves a bioavailability.

Abstract: A method of modulating cytokine mediated hepatic injury by administering deltorphins to a mammal. Deltorphin I SEQ ID NO:1, deltorphin II SEQ ID NO:2 or combinations of deltorphins I SEQ ID NO:1 and II SEQ ID NO:2 may be administered. A deltorphin concentration in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade in a murine model of septic shock. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.

Abstract: A process for the preparation of a protein solution is described which is not prone to flock or particle formation even on heat treatment, the heat treatment being carried out in a glass vessel which has been rinsed out beforehand with a detergent solution and then with distilled water or another detergent-free solvent.

Abstract: A compound comprising a ligand portion which has binding affinity for an opioid receptor, and a therapeutically or diagnostically effective group selected from radionuclide chelating agents, fluorochromes, toxins, drugs, polyboron moieties, proteins, biological response modifiers, chemical moieties capable of binding to other molecules of interest, and radioisotopes selected from therapeutically effective alpha and beta emitters, and diagnostically effective gamma emitters. The compound may be used in a method of treating cancer, and in a method of imaging opioid receptors either inside or outside of the central nervous system.

Abstract: This invention relates to novel opioid peptides for the treatment of pain as well as a method for the preparation thereof and pharmaceutically acceptable compositions comprising these peptides. The invention also relates to methods for controlling pain in patients using compositions of the invention and the use of said compounds in the preparation of formulations effective in pain treatment. The peptides of this invention have a high degree of selectivity for the &mgr;-opioid receptor. The peptides of the present invention are particularly well-suited as analgesic agents acting substantially on peripheral &mgr;-opioid receptors. Because these peptides act peripherally, they substantially avoid producing side effects normally associated with central analgesic action.

Abstract: This invention relates to certain peptides and linear and cyclic analogs thereof that bind to the mu (morphine) opiate receptor with higher affinity, selectivity and potency than currently available peptides. This invention also relates to pharmaceutical preparations containing an effective amount of the peptides or salts thereof, and methods for providing analgesia, relief from gastrointestinal disorders such as diarrhea, and therapy for drug dependence containing a pharmaceutically effective amount of the peptides.

Abstract: Disclosed are lanthionine bridged peptides having the structure methods of their preparation and their use as pharmacologically active agents.

Abstract: The invention concerns a process for the enzymatic preparation of protected di- and oligopeptides and the separation of the protective groups used. The process according to the invention enables peptides to be synthesized simply and economically and the protective group to be separated carefully. The process comprises three reaction steps: 1. Preparation of N-carbamoyl amino acid or N-carbamoyl amino acid derivatives; 2. Formation of the peptide bond between the carbamoyl-protected electrophile and nucelophile; and 3. Separation of the carbamoyl-protective group.

Abstract: The present invention is related to the treatment and prevention of cancer including particularly gastrointestinal cancer. More specifically, the present invention describes the use of naltrexone, naloxone and the pentapeptide growth factor [Met.sup.5 ]-enkephalin to inhibit and arrest the growth of cancer. Such efficiency has been discovered to be a consequence of the functional manipulation of the zeta (.zeta.) opioid receptor through endogenous [Met.sup.5 ]-enkephalin. This receptor has been determined to be present in growing cancers such as pancreatic and colon cancer, for example.

Abstract: The invention provides biologically active compounds of the formula: ##STR1## where R.sub.1 is a light-emitting moiety and R.sub.7 is a peptide of between 2 and 200 amino acids. X is selected from the group including .dbd.O, .dbd.S, --OH, .dbd.C.tbd.O, .dbd.NH, --H, --OR, --NR, --R, --R.sub.3 R.sub.4, wherein each R, R.sub.4 and R.sub.3, independently, is H or a C1-C6 branched or unbranched, substituted or unsubstituted, alkyl. The compounds are both biologically active and optically detectable. The peptide is chemically attached to the light-emitting moiety at an amino acid position which is not involved in binding to the peptide's receptor. In this way, the peptide's affinity for its receptor is not significantly decreased, and the compound retains high biological activity and can be easily detected using standard optical means.

Abstract: Disclosed are lanthionine peptides having the structure ##STR1## methods of their preparation and use as pharmacologically active agents.

Abstract: Peptide derivatives usable as zinc endopeptidase 24-15 inhibitors.These peptide derivatives have the following amino acid sequence:-Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) Xaa'-Yaa'-Zaa'-in which .psi.(PO.sub.2 CH.sub.2) indicates that the peptide bond (CONH) has been replaced by the phosphine bond (PO.sub.2 CH.sub.2), Xaa' and Zaa', which can be the same or different, in each case represent a natural amino acid or an amino pseudo-acid and Yaa' represents Arg or Lys.As examples of such derivatives, reference can be made to those of formula:Z-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Gly-Arg-MetOHZ-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Ala-Arg-MetOHZ-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Ala-Arg-PheOHwith Z representing the benzyloxycarbonyl group.

Abstract: The invention is directed to human serum albumin-porphyrin (HSA-P) complexes which are capable of reversible oxygen binding and their uses. These complexes may be used in applications requiring physiological oxygen carriers such as in blood substitute solutions, or in applications requiring plasma expanders. Methods for the production of these complexes are provided. In a specific example, HSA-P complexes are shown to exhibit reversible oxygen binding. In another example, the HSA-P complex does not exhibit appreciable vasoactivity.

Abstract: The isolation, cloning and characterization of a human gene related to but distinct from EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes have also been described.

Abstract: Compounds of the formula I as well as methods for their preparation, their pharmaceutical preparations and their use. ##STR1## The compounds of formula I are useful in therapy, especially as analgesics and as immunosuppresive agents.

Abstract: A physiologically active substance well capable of permeating biomembrane according to the present invention is represented by: ##STR1## where R represents a residue of a physiologically active substance comprising a peptide, amino acid, aliphatic amine having a phenol skeleton, amino sugar, nucleoside or lactam compound and a residue of physiologically active derivative thereof. The biomembrane permeability of a substance with poor biomembrane permeability can be improved by introducing an adamantyl group to the physiologically active substance.

Abstract: The present invention relates to a novel method for making a predetermined, desired peptide in transgenic animals and can be advantageously used for the production of large quantities of the desired peptide. More particularly, the invention concerns the engineering of a transgenic animal having an artificial gene, which is controlled by globin locus control region (LCR) and which encodes a fusion protein, in which the desired peptide is joined via a cleavable peptide linker to a globin polypeptide. The erythrocytes of the transgenic animal express the fusion globin which is incorporated into hemoglobin produced by the host cell. The desired peptide can be obtained from a hemolysate of the red cells of the transgenic animals by enzymatic or chemical cleavage at the linker.

Abstract: A method of treating a patient having a panic disorder, the patient having an elevated CCK peptide plasma level, by lowering the plasma CCK peptide level of the patient. A further method provides a diagnosis of panic disorder in a patient by detecting if that patient's plasma contains elevated CCK peptide levels. A further method determines the efficacy of the drug for the treatment of panic disorder by detecting the ability of the drug to lower elevated CCK peptide levels in a model for panic disorder. Additionally, a method of dosing a patient having elevated CCK peptide levels with an antipanic disorder drug is characterized by administering the drug to a patient and monitoring the lowering of the elevated plasma CCK peptide levels of the patient.

Abstract: Processes for synthesizing polypeptides containing substantially non-antigenic polymers, preferably poly(alkylene glycols) in specifically predetermined sites are disclosed. Polypeptides prepared by such processes acre also disclosed.

Abstract: The present invention relates to analgesic enkephalin derivatives represented by the following formula:Tyr-A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 SEQ ID NO:5 (1)and the acid salts thereof, wherein Tyr is L-tyrosine, A.sub.1 or A.sub.2 is a glycine, and that which is not a glycine is an optically active trifluoro amino acid of the formula: ##STR1## wherein n is an integer from 1-3 and m is 1 or 2; A.sub.3 is L-Phenylalanine, or N-methyl-(L)-phenylalanine, and A.sub.4 is L-Methionine, L-Met-OH, L-Met-ol or L-Met-NH.sub.2.

Abstract: The present invention provides substituted cyclic pentapeptide compounds of general Formula I: ##STR1## and the pharmaceutically-acceptable slats, esters and amides thereof, which are useful for inducing analgesia in animals, pharmaceutical compositions comprising a pharmaceutically-acceptable carrier and a compound of Formula I, and a method for inducing analgesia in an animal in need thereof comprising administering a therapeutically-effective amount of a compound of Formula I to the animal.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical agent conjugate wherein the antibody is reactive with a transferrin receptor. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical agent and method for treating hosts afflicted with a disease associated with a neurological disorder.

Abstract: The invention relates to enkephalin analogs of the formula ##STR1## wherein in case of X is D-Val, D-Phe, Pro, D-Met, D-Met(O), D-Leu, D-Glu, D-Glu(Obzl), D-Lys, D-Lys(Z), or D-Arg,Y is Gly or Phe; andR isa) a direct bond,b) an alkylene group having from 1 to 6 carbon atoms,c) o-, m-, or p-phenylene group,d) a cycloalkane; orwherein in case ofX is D-Ala,Y is Phe; andR isa) a direct bond,b) an alkylene group having from 1 to 6 carbon atoms,c) o-, m-, or p-phenylene group, ord) a cycloalkane,its salts and hydrates, as well as a therapeutic composition containing at least one of the enkephalin analogs, as an effective component.

Abstract: Cyclic disulfide and linear dynorphin Dyn A.sub.1-11 and dynorphin Dyn A.sub.1-13 analogs which are highly specific for .kappa. opioid receptors. These analogs are useful in pharmaceutical compositions and for the analysis of opioid receptor/ligand interactions.

Abstract: The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug.In a preferred embodiment, the carrier is 4, 7, 10, 13, 16, 19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be digested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.

Abstract: Chimeric peptides adapted for delivering neuropharmaceutical agents, such as neuropeptides into the brain by receptor-mediated transcytosis through the blood-brain barrier. The chimeric peptides include a peptide which by itself is capable of crossing the blood-brain barrier by transcytosis at a relatively high rate. The transportable peptide is conjugated to a hydrophilic neuropeptide which by itself is transportable only at a very low rate into the brain across the blood-brain barrier. The resulting chimeric peptide is transported into the brain at a much higher rate than the neuropeptide alone to thereby provide an effective means for introducing hydrophilic neuropeptides into the brain through the blood-brain barrier.

Abstract: Chimeric peptides adapted for delivering neuropharmaceutical agents, such as neuropeptides into the brain by receptor-mediated transcytosis through the blood-brain barrier. The chimeric peptides include a peptide which by itself is capable of crossing the blood-brain barrier by transcytosis at a relatively high rate. The transportable peptide is conjugated to a hydrophilic neuropeptide which by itself is transportable only at a very low rate into the brain across the blood-brain barrier. The resulting chimeric peptide is transported into the brain at a much higher rate than the neuropeptide alone to thereby provide an effective means for introducing hydrophilic neuropeptides into the brain through the blood-brain barrier.

Abstract: The present invention provides novel peptides of formula (I):R--(X.sup.1).sub.m --(X.sup.2).sub.n --X.sup.3 --X.sup.4 --X.sup.5 --X.sup.6 --X.sup.7 --(X.sup.8).sub.p --(X.sup.9).sub.q --R.sup.1 (I)together with their salts, esters, amides, N-alkylamides and N,N-dialkylamides and acid addition salts thereof.These compounds exhibit morphine agonist activity in both in vitro and in vivo tests and may be used in the treatment of mammals in the fields of both human and veterinary medicine in any condition where an agent with a morphine-like effect is indicated.