Structural requirements for opioid activity of analogues of the enkephalins.

摘要: Structure-activity relations of a series analogues the two endogenous morphine-like peptides, leucine-enkephalin and methionine-enkephalin are examined on basis (a) effects mouse vas deferens guinea pig ileum (b) affinities for rat brain opiate receptor. In deferens, metabolism peptides by proteolysis is not major influence activity. contrast, however, receptor preparations contain an abundance proteolytic enzymes, which can be minimized conducting binding assays at 0 degrees C in presence bacitracin. The potentiation biological activity affinity replacing Gly$^{2}$ residue natural enkephalins D-Ala, discussed both terms increased stability Tyr-D-Ala bond to aminopeptidases stabilization peptide conformation as present receptor-peptide complex. substitution Leu$^{5}$- or Met$^{5}$-residue corresponding D-amino acid contributes little stability, emphasizes that predominating site occurs Tyr$^{1}$-Gly$^{2}$ bond. Of described, [D-Ala$^{2}$, D-Leu$^{5}$]-enkephalin most active three assay systems, preparations. Substitutions respective acids D-Tyr D-Phe positions 1 4 reduce potency emphasize importance stereochemical acceptability these positions. promotion examined, particularly with respect implied conformations. experimental data have been analysed relative metabolic conformational factors.