通过核磁共振在水溶液中对一种强效SSTR3选择性生长抑素类似物进行构象分析。

Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution.

作者信息

Gairí Margarida, Saiz Pilar, Madurga Sergio, Roig Xavier, Erchegyi Judit, Koerber Steven C, Reubi Jean Claude, Rivier Jean E, Giralt Ernest

机构信息

NMR Facility, Serveis Cientificotècnics, University of Barcelona, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.

出版信息

J Pept Sci. 2006 Feb;12(2):82-91. doi: 10.1002/psc.743.

DOI:10.1002/psc.743

PMID:16365912

Abstract

The three-dimensional structure of a potent SSTR3-selective analogue of somatostatin, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-Agl(8)(N(beta) Me, 2-naphthoyl)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-Agl(8)(N(beta) Me, 2-naphthoyl)]-SRIF) (peptide 1) has been determined by (1)H NMR in water and molecular dynamics (MD) simulations. The peptide exists in two conformational isomers differing mainly by the cis/trans isomerization of the side chain in residue 8. The structure of 1 is compared with the consensus structural motifs of other somatostatin analogues that bind predominantly to SSTR1, SSTR2/SSTR5 and SSTR4 receptors, and to the 3D structure of a non-selective SRIF analogue, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-2Nal(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-2Nal(8)]-SRIF) (peptide 2). The structural determinant factors that could explain selectivity of peptide 1 for SSTR3 receptors are discussed.

摘要

通过水中的¹H NMR和分子动力学（MD）模拟，已确定了一种强效的生长抑素SSTR3选择性类似物环（3 - 14）H - Cys(3)-Phe(6)-Tyr(7)-D - Agl(8)(NβMe, 2 - 萘甲酰基)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH（去AA(1, 2, 4, 5, 12, 13)[Tyr(7), D - Agl(8)(NβMe, 2 - 萘甲酰基)] - SRIF）（肽1）的三维结构。该肽存在两种构象异构体，主要区别在于第8位残基侧链的顺/反异构化。将肽1的结构与主要结合SSTR1、SSTR2/SSTR5和SSTR4受体的其他生长抑素类似物的共有结构基序，以及一种非选择性SRIF类似物环（3 - 14）H - Cys(3)-Phe(6)-Tyr(7)-D - 2Nal(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH（去AA(1, 2, 4, 5, 12, 13)[Tyr(7), D - 2Nal(8)] - SRIF）（肽2）的三维结构进行了比较。讨论了可以解释肽1对SSTR3受体选择性的结构决定因素。