Dehydro‐enkephalins. III. Synthesis and biological activity of [ΔAla2, Leu5]‐enkephalin

Abstract

[.DELTA.Ala2, Leu5]-enkephalin was prepared and was more active than the parent saturated enkephalin in a binding assay using rat brain membranes and [3H]dihydromorphine as a tracer. In a comparison of potencies against [3H]dihydromorphine and [3H]-[D-Ala2, D-Leu5]-enkephalin as tracers, [.DELTA.Ala2, Leu5]-enkephalin showed preference for .mu. opiate receptors, possibly due to the hydrophobicity of the .DELTA.Ala2 residue. A synthetic tetrapeptide enkephalin [.DELTA.Ala2]-desLeu5-enkephalin had weak activity and high selectivity for the .mu. receptors. O-Acylation of a serine residue in the peptide was achieved by coupling between the peptide and a carboxylic acid using N,N''-dicyclohexylcarbodiimide and a catalytic amount of 4-dimethylaminopyridine.