Conformational studies of diastereomeric cyclic enkephalins by ¹H‐NMR and computer simulations

Abstract

Abstract We report the solid‐phase synthesis and conformational analysis of a 14‐membered, cyclic enkephalin analog, HTyrc[ D A 2 buGlyPhe 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, HTyrc[ D A 2 buGlyPheLeu] [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.