NONPEPTIDE BETA-TURN MIMETICS OF ENKEPHALIN

The design and synthesis of a conformationally restricted peptide mimetic of the endogenous opiate peptide leucine enkephalin is described. This mimetic incorporates a nonpeptide beta-turn prosthetic unit; conformational analysis indicates that the active isomer exhibits a conformation closely corresponding to that of a highly potent, delta-selective enkephalin analog, Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE, Pen=Penicillamine). Preliminary pharmacological investigation indicated that one isomer of the mimetic species exhibits significant in vivo analgesic activity, despite relatively low in vitro binding affinity.