Structure-activity relationship of the novel bivalent and C-terminal modified analogues of endomorphin-2.
Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is a putative endogenous mu-opioid receptor ligand. To develop potent analgesics with less side effects related to it, we used the methods of dimerization and C-terminal modification. Through dimerization we got the 'balanced agonists' with potent analgesic activity and we have developed the structure-activity relationship between the selectivity and the distance of the two tyrosine pharmacophores. Modification at the C-terminal increased the selectivity of endomorphin-2 to mu-opioid receptor with binding affinity conserved.
Gao
Yanfeng
Y
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Liu
Xin
X
Wei
Jie
J
Zhu
Beibei
B
Chen
Qiang
Q
Wang
Rui
R
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry
D000700:Analgesics; D008024:Ligands; D009842:Oligopeptides; C105294:endomorphin 2; D014443:Tyrosine