Structure-activity relationships of novel endomorphin-2 analogues with N-O turns induced by alpha-aminoxy acids.
Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2, EM-2) is a putative endogenous mu-opioid receptor ligand. To study the structure-activity relationship against its receptor, we introduced N-O turns into EM-2 and got the analogues with potent affinities for mu-opioid receptor. Our results indicated that N-O turn structures at the Pro2-aminoxy-Phe3 position of EM-2 analogues played important roles for their affinities. These novel analogues with N-O turns provided a new approach to develop potent analgesics related to EM-2.
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Jie
J
Wei
Xuan
X
Shao
Maozhen
M
Gong
Beibei
B
Zhu
Yuxin
Y
Cui
Yanfeng
Y
Gao
Rui
R
Wang
D000596:Amino Acids / Q000737:chemistry*; D000598:Amino Acids, Cyclic; D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship; D013552:Swine; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000701:Analgesics, Opioid; D008024:Ligands; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C105294:endomorphin 2