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Conformational studies of diastereomeric cyclic enkephalins by 1 H‐NMR and computer simulations
Author(s) -
Mierke Dale F.,
Lucietto Pierluigi,
Goodman Murray,
Schiller Peter W.
Publication year - 1987
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360260909
Subject(s) - chemistry , diastereomer , enkephalin , stereochemistry , cyclic peptide , selectivity , receptor , opioid receptor , molecular model , opioid , peptide , biochemistry , catalysis
We report the solid‐phase synthesis and conformational analysis of a 14‐membered, cyclic enkephalin analog, HTyrc[ D A 2 buGlyPhe D Leu] (where A 2 bu represents α,γ‐diaminobutyric acid). The results from the guinea pig ileum (GPI) and mouse vas deferens (MVD) assays show that the analog, though active, has little selectivity for the μ or δ opioid receptors. Conformational analysis is carried out using 1 H‐nmr and computer simulations, including molecular dynamics and energy minimizations. The results obtained here are compared with the findings of our studies carried out on the μ‐receptor‐selective diastereomer, HTyrc[ D A 2 buGlyPheLeu] [N. Mammi, M. Hassan, and M. Goodman (1985) J. Am. Chem. Soc. 107 , 4008–4013]. This comparison allows for insight into the regiospecificity of these cyclic enkephalin analogs.