Dynorphin(1-13) has been previously reported to antagonize the analgesia induced by narcotics in naive hosts. Novel compounds are provided which differ from dynorphin(1-13) by neither potentiating nor antagonizing narcotics, such as morphine, in naive animals. In tolerant hosts the new compounds potentiate narcotic or peptide induced analgesia, and in addition are less susceptible to degradation than dynorphin(1-13). Particularly preferred of the new compounds are polypeptides having ten amino acids with nitrogen containing moieties at both termini.

Dynorphin amide analogs

Novel peptides of the invention are dynorphin analogues and have similar activity to endogenous dynorphin, but are des-Tyr or des-Tyr-Gly with respect to endogenous dynorphin. The novel peptides have therapeutic uses, such as administration to a host tolerant to a narcotic analgesic in order to potentiate activity of the narcotic analgesic and/or to block withdrawal symptoms.

Des-tyr dynorphin analogues

Dynorphin A analogues truncated at the N-terminus are used as analgesics to relieve pain, such as painful neuropathies where the analgesic effect is not opioid. Novel, analgesic peptides that are des-(Tyr-Gly-Gly) with respect to endogenous dynorphin are also disclosed.

Analgesic method with dynorphin analogues truncated at the n-terminus

A method for treating inflammatory conditions is provided in which a peptide is administered in an amount effective to decrease inflammation, with the peptide having the sequence: G-G-F-L-R-R-I-R-P-K-L-K-W-D-N-Q (SEQ ID NO:1), G-G-F-L-R-R-I-R-P-K-L-K-W-D-N-Q-NH2 (SEQ ID NO:2), Ac-R-R-I-R-P-K-L-NH2 (SEQ ID NO:3), or Ac-R-R-I-R-P-K-l-NH2 (SEQ ID NO:4).

Anti-inflammatory composition and method with des-tyr dynorphin and analogues

The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugate comprises a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Methods of altering the binding affinity of a peptide to its receptor

Novel opioid compounds are provided having a phenolic hydroxyl and a pentet of alternating basic hydrophilic and hydrophobic groups derived from basic amino acids and hydrophobic amino acids. Desirably, the pentet, usually sextet, is separated from the phenolic ring by at least about 3 atoms in a chain, preferably at least about 15 atoms in a chain and not more than about 30 atoms in a chain (for rings one will take the average of the shortest and longest distances). Particularly, a polypeptide is provided having tyrosyl at the amine end, desirably as the first amino acid of leu- or met-enkephalin and a sextet of alternating basic hydrophilic and hydrophobic amino acids spaced from the enkephalin by at least about one amino acid. Desirably, the polypeptide is at least 1,200 molecular weight and under about 2,500 molecular weight.

Novel polypeptide analgesics

Novel compounds are provided each having a chain of at least five, and usually a sextet of, alternating basic hydrophilic and hydrophobic units derived from basic amino acids and hydrophobic amino acids. Preferably, such a compound additionally contains a phenolic group and, desirably, is separated from the phenolic group by a further chain having at least 3 atoms, preferably at least 15 atoms, and not more than about 30 atoms in the further chain (the further chain may itself include a ring, when one will take the average of the shortest and longest distances). In particular, a polypeptide is provided having tyrosyl at an amine end thereof, desirably as the first amino acid of leu-or met-enkephalin and a sextet of alternating basic hydrophilic and hydrophobic amino acids spaced from the enkephalin by at least one amino acid. Desirably, the polypeptide has a molecular weight of at least 1.200 less than about 2,500.

Polypeptides, antisera containing them and methods of their use

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Novel polypeptide analgesics

Polypeptides, antisera containing them and methods of their use