Conformational analysis of endomorphin-2 analogs with phenylalanine mimics by NMR and molecular modeling

被引：19
作者：
Shao, Xuan
Gao, Yanfeng
Zhu, Chuanjun
Liu, Xuehui
Yao, Jinlong
Cui, Yuxin [1 ]
Wang, Rui
机构：
[1] Lanzhou Univ, Sch Life Sci, Inst Biochem & Mol Biol, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China
[2] Peking Univ, Med & Hlth Anal Ctr, Sch Pharmaceut Sci, State Key NAt & Biomimet Drugs, Beijing 100083, Peoples R China
[3] Chinese Acad Sci, Lanzhou Inst Chem Phys, State Key Lab Oxosynth & Selct Oxidat, Lanzhou 730000, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 10期
基金：
中国国家自然科学基金;
关键词：
endomorphin-2; conformation; NMR; molecular modeling;
D O I：
10.1016/j.bmc.2007.02.050
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 H-1 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 mu-opioid receptor. (c) 2007 Elsevier Ltd. All rights reserved.
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收藏
页码：3539 / 3547
页数：9
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