Conformational features responsible for binding of cyclic analogues of enkephalin to opioid receptors. I. Low-energy peptide backbone conformers of analogues containing Phe4.

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 mu- and delta-types. They included [D-Cys2, L-Cys5]- and [D-Cys2, D-Cys5]-enkephalinamides showing moderate preference for mu-receptors, the delta-selective compounds [D-Pen2, L-Pen5] and [D-Pen2, D-Pen5]-enkephalins and Tyr-D-Lys-Gly-Phe- analogue possessing very high affinity to receptors of the mu-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.