Document Report Card

ID: ALA1154618

Journal: J Med Chem

Title: Agonist vs antagonist behavior of delta opioid peptides containing novel phenylalanine analogues in place of Tyr(1).

Authors: Berezowska I, Chung NN, Lemieux C, Wilkes BC, Schiller PW.

Abstract: The novel phenylalanine analogues 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Bcp) and 2',6'-dimethyl-4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Dbcp) were substituted for Tyr(1) in the delta opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH; Tic = tetrahydroisoquinoline-3-carboxylic acid). Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high delta antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites. The dipeptide H-Dbcp-Tic-OH was a highly selective delta antagonist with subnanomolar delta receptor affinity.

CiteXplore: 19827750

DOI: 10.1021/jm9004913