Conformation of the tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 deduced from two-dimensional 1H-NMR and conformational energy calculations is related to its affinity for NK1-receptor

被引:12
作者
Millet, R [1 ]
Goossens, L [1 ]
Goossens, JF [1 ]
Chavatte, P [1 ]
Bertrand-Caumont, K [1 ]
Houssin, R [1 ]
Hénichart, JP [1 ]
机构
[1] Univ Lille 2, Inst Chim Pharmaceut Albert Lespagnol, F-59006 Lille, France
关键词
conformational analysis; neurokinin A; NMR; substance P;
D O I
10.1002/psc.326
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
Chemical modifications of dual NK1/NK2 ligand Cbz-Gly-Leu-Trp-OBzl(CF3)(2) (1) enabled us to create a high NK, selective ligand Cbz-Pro-Leu-Trp-OBzl(CF3)(2) (2). A determination of the conformational behavior of tripeptide 2 in solution is described. The 1D and 2D H-1-NMR techniques (COSY and ROESY) were used to assign resonances. Observed interproton distance restraints were considered to characterize conformational behavior. Spectral data indicate that tripeptide 2 presents a rigidified structure in DMSO stabilized by H-bond in two gamma -turns. Agreement with experimental data was obtained by averaging the H-1-NMR parameters over several combinations of low-energy conformations. Copyright (C) 2001 European Peptide Society and John Wiley & Sons, Ltd.
引用
收藏
页码:323 / 330
页数:8
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