Original endomorphin-1 analogues exhibit good analgesic effects.

Yanjing Wu, Xinyi Zhao, Yongan Gan, Xuehong Zhang, Hongbin Wei, Lewei Wang, Xiaolei Liang, Xuelin Gao, Ying Liu, Junping Hu, Yiqing Wang

Bioorganic & medicinal chemistry letters 2017 Apr 01

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A new class of endomorphin-1 analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4 was chlorinated, D-Ala-Gly Substituted L-Pro2. Their bioactivities were measured by radioligand binding assay, metabolic stability and the tail-flick test. In radioligand binding assays, analogue GAGPC (Nα-Amidino-Tyr-D-Ala-Gly-Trp-p-Cl-Phe-NH2), shown a μ-opioid receptor affinity about 1.42-fold higher and a 2.51-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGPC had the longest half-lives which was 284min 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Citation

Yanjing Wu, Xinyi Zhao, Yongan Gan, Xuehong Zhang, Hongbin Wei, Lewei Wang, Xiaolei Liang, Xuelin Gao, Ying Liu, Junping Hu, Yiqing Wang. Original endomorphin-1 analogues exhibit good analgesic effects. Bioorganic & medicinal chemistry letters. 2017 Apr 01;27(7):1557-1560