Original endomorphin-1 analogues exhibit good analgesic effects

A new class of endomorphin-1 analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe(4) was chlorinated, D-Ala-Gly Substituted L-Pro(2). Their bioactivities were measured by radioligand binding assay, metabolic stability and the tail-flick test. In radioligand binding assays, analogue GAGPC (N-alpha-Amidino-Tyr-D-Ala-Gly-Trp-p-Cl-Phe-NH2), shown a mu-opioid receptor affinity about 1.42-fold higher and a 2.51-fold higher delta-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGPC had the longest half-lives which was 284 min and 53-fold higher than that of EM-1. In the tail-flick test in mice, GAGPC chloride modification increases the lipid content of the drug, thus increases the permeability of the blood brain barrier, and has a higher analgesic activity. It might be of importance in potential application as drug candidates as analgesic. (C) 2017 Elsevier Ltd. All rights reserved.