METHIONINE ENKEPHALIN AND ISOSTERIC ANALOGUES

Abstract

Biological activities are reported for two different types of analogues of methionine enkephalin. Cyclic analogues, bridged between the amino- and carboxy- terminals of the parent peptide, are inactive. In contrast, significant levels of activity are displayed by linear isosterically modified analogues in which the Tyr1-Gly2 peptide bond is replaced by either -CH2NH- or -CH2CH2-. Similar replacements of the Gly2-Gly3 peptide bond yield compounds with much reduced potency. These modifications serve as useful probes of the receptor conformation. Based on these findings, a model is proposed for interaction between enkephalin and its receptor.