Opioid receptor binding and antinociceptive activity of the analogues of endomorphin-2 and morphiceptin with phenylalanine mimics in the position 3 or 4.
Endomorphin-2 (EM-2) and morphiceptin are the same class of putative mu-opioid receptor ligands. To investigate the effectiveness of phenylglycine (Phg, L or D) and homophenylalanine (Hfe) as the surrogates of phenylalanine in the position 3 and/or 4 of them, a series of their analogues were synthesized. Opioid receptor binding affinities were determined. Two analogues, [Hfe3]EM-2 and [Phg4] (EM-2/morphiceptin), showed different but potent antinociceptive activity in mouse hot-plate test, the results combined with their half-lives of degradation by mouse brain homogenate could also present some evidence to the in vivo degradative mechanism of EM-2.
Gao
Yanfeng
Y
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Liu
Xin
X
Liu
Weixia
W
Qi
Yuanming
Y
Liu
Xuefeng
X
Zhou
Yifeng
Y
Wang
Rui
R