Dynorphin a analogs with bradykinin receptors specificity for modulation of neuropathic pain
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorsYeon Sun LEE, Victor J. HRUBY, Frank PORRECA, Josephine LAI
Life of this patent
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Abstract
Described are Dynorphin A analog compounds and uses thereof for treating pain in humans and lower animals by administering to a human or lower animal in need of treatment. The compounds interact with the bradykinin receptor to relieve pain. Preferred compounds are amphipathic [Des-Arg7]-dynorphin A peptide analogs and specific cyclic dynorphin A peptide analogs.
Claims19
A [des-Arg7]-dynorphin A analog compounds having the formula
- R1-(AA1-AA2)1-Pro-AA2-(AA1-AA2)m
- wherein R1 is Phe, Phe(X), Trp, D-Phe, D-Phe(X), D-Trp, Gly-Phe, Gly-Phe(X), or Gly-Trp and same as AA2 if 1=0 and N-terminus is acetylated or a free amine, AA1 is Ile, Leu, Nle, Val, Ala, D-Leu, D-Nle, D-Val, D-Ala, or any other hydrophobic amino acids, AA2 is Arg, Lys, His, Orn, or any other basic amino acids, and the AA2 terminus is an acid, land m are 0, 1, or 2.
A cyclic dynorphin A analog compounds having the formula
- c[R1-(AA2-AA1)n-AA2-AA3]-AA2
- wherein R1 is Phe, Phe(X), Trp, D-Phe, D-Phe(X), D-Trp, Gly-Phe, Gly-Phe(X), or Gly-Trp AA1 is Ile, Leu, Nle, Val, Ala, D-Ile, D-Leu, D-Nle, D-Val, D-Ala, or any other hydrophobic amino acid, AA2 is Arg, Lys, His, Orn, or any other basic amino acids and the AA2 terminus is an acid, AA3 is Asp, Glu, or any other amino acid having a side chain acid group, n is 1, or 2.
A cyclic dynorphin A analog having the formula
- (AA2-AA1)o-c[AA3-AA1p-(AA2-AA1-AA2)q-AA1p-AA3]-AA2
- wherein AA1 is Ile, Leu, Nle, Val, Ala, D-Ile, D-Leu, D-Nle, D-Val, D-Ala, or any other hydrophobic amino acid, AA2 is Arg, Lys, His, Orn, or any other basic amino acids and the AA2 terminus is an acid, AA3 is Asp, Glu, Lys, or any other amino acid having a side chain acid group or amino group, o is 0, or 1, p is 0, or 1, q is 1, or 2.
The cyclic dynorphin A analog compounds according to claim 6, wherein the counterpart amino acid is Lys/Asp, Asp/Lys.
The process for treating pain in humans and lower animals, which comprises administering to a human or lower animal in need of treatment a compound that interacts with the bradykinin receptor as a antagonist to relieve pain.
Dependencies are inferred from the claim text.