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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Berezowska I,Chung NN,Lemieux C,Wilkes BC,Schiller PWdoi
10.1021/jm9004913subject
Has Abstractpub_date
2009-11-12 00:00:00pages
6941-5issue
21eissn
0022-2623issn
1520-4804journal_volume
52pub_type
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