Conformational analysis of endomorphin-2 analogs with phenylalanine mimics by NMR and molecular modeling.
We investigated a series of conformations of endomorphin-2 (EM-2) analogs substituted by phenylglycine (Phg) and homophenylalanine (Hfe) in the position 3 or 4 by two-dimensional (1)H NMR spectroscopy and molecular modeling. Evaluating the aromatic interactions and the dihedral angles in these phenylalanine mimics, we have observed that the conformations in trans isomer have varied from extended to folded as bioactivity decreases. It is suggested that the flexibility of aromatic side chain affects the backbone of EM-2 to adopt folded structures, which may block the ligands in binding to micro-opioid receptor.
Shao
Xuan
X
State Key Laboratory of Applied Organic Chemistry, Institute of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou 730000, People's Republic of China.
Gao
Yanfeng
Y
Zhu
Chuanjun
C
Liu
Xuehui
X
Yao
Jinlong
J
Cui
Yuxin
Y
Wang
Rui
R
D000596:Amino Acids / Q000737:chemistry; D004121:Dimethyl Sulfoxide; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry*; D017450:Receptors, Opioid, mu / Q000187:drug effects
D000596:Amino Acids; D009842:Oligopeptides; D010455:Peptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C105294:endomorphin 2; D010649:Phenylalanine; D004121:Dimethyl Sulfoxide