SYNTHESIS AND BINDING PROFILES OF ENDOMORPHIN-2 ANALOGUES CONTAINING A CONFORMATIONALLY CONSTRAINED MOIETY

摘要

Endomorphin-2 (EM-2: H-Tyr-Pro-Phe-Phe-NH2), an endogenous opioid peptide isolated from bovine and human brain, has high affinity and selectivity for the mu-opioid receptor and produces potent and prolonged analgesia in mice . In this presentation, the synthesis of EM-2 analogues containing a conformationally constrained moiety and examination of their opioid receptor binding profiles were conducted in order to obtain more potent agonist or antagonist with stability against dipeptidyl peptidase IV (DPP IV). The ethylene-bridged Phe-Phe unit (eb[Phe-Phe]) or piperidine carboxylic acid (Pic) was employed in lieu of Pro.