Conformational features responsible for binding of cyclic analogues of enkephalin to opioid receptors

Abstract

Low-energy peptide backbone conformers were found by means of energy calculation for several cyclic analogues of enkephalin in an attempt to assess models for receptor-bound conformations for opioid receptors of the p-and &types. They included [D-CYS', ~-Cys']-and [D-CYS', ~-Cys~]-enkephalinamides showing moderate preference for preceptors, the &selective compounds [D-Pen', pen'] and [D-Pen', ~-Pen~]-enkephalins and T y r -D -L y m analogue possessing very high affinity to receptors of the p-type. The low-energy conformers obtained for these analogues were in good agreement with the results of calculations by other authors and with experimental evidence. All of the analogues contain a Phe residue in position 4 of the peptide chain which facilitates the eventual search for geometrical similarity between the low-energy backbone conformers of different analogues in question.