title: Original endomorphin-1 analogues exhibit good analgesic effects.
abstract: A new class of endomorphin-1 analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4was 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.
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Gan
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China; Key Laboratory for Reproductive Medicine and Embryo, Gansu Province, Lanzhou 730000, China.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wei
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China; Key Laboratory for Reproductive Medicine and Embryo, Gansu Province, Lanzhou 730000, China.
authors.forename: Lewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China; Key Laboratory for Reproductive Medicine and Embryo, Gansu Province, Lanzhou 730000, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liang
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Gao
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China; Key Laboratory for Reproductive Medicine and Embryo, Gansu Province, Lanzhou 730000, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Hu
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, China; Key Laboratory for Reproductive Medicine and Embryo, Gansu Province, Lanzhou 730000, China. Electronic address: 511508864@qq.com.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006207:Half-Life; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; C000621526:Nalpha-amidino-Tyr-Ala-Gly-Trp-p-Cl-Phe-NH2; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D009270:Naloxone
keywords: Analgesic activity; Endomorphin-1 analogues; Metabolic stability