α-甲基取代对线性促性腺激素释放激素拮抗剂类似物构象的影响。

Effects of C alpha-methyl substitution on the conformation of linear GnRH antagonist analogs.

作者信息

Liff M I, Kopple K D, Tian Z, Roeske R W

机构信息

Philadelphia College of Textiles and Science, Pennsylvania.

出版信息

Int J Pept Protein Res. 1994 May;43(5):471-6. doi: 10.1111/j.1399-3011.1994.tb00546.x.

DOI:10.1111/j.1399-3011.1994.tb00546.x

PMID:8070971

Abstract

We have examined the effect of C alpha-methyl groups on the conformational ensemble of GnRH analog peptides by comparing 1H 2D NMR data from two analogs, Ac-D-Nal1-D-4-Cl-C alpha-Me-Phe2-D-Pal3-Ser4-Tyr5-D-Arg6-Leu7-Arg8-Pro9-D-Al a10- NH2 (1) and Ac-D-Nal1-D-4-Cl-C alpha-Me-Phe2-D-Pal3-Ser4-C alpha-Me-Tyr5-D-Arg6- Leu7-C alpha-Me-Arg8-Pro9-D-Ala10-NH2 (2). The two additional C alpha-methyl groups in residues 5 and 8 of 2 do not influence significantly the pattern of the observable main chain NOE intensities, or of the backbone HN proton chemical shifts, which indicates that they do not produce global changes in the conformational ensemble of the peptide. A local change induced by the substitution was observed in the conformation at D-Arg8-Pro9.

摘要

我们通过比较两种类似物Ac-D-Nal1-D-4-Cl-Cα-Me-Phe2-D-Pal3-Ser4-Tyr5-D-Arg6-Leu7-Arg8-Pro9-D-Ala10-NH2（1）和Ac-D-Nal1-D-4-Cl-Cα-Me-Phe2-D-Pal3-Ser4-Cα-Me-Tyr5-D-Arg6-Leu7-Cα-Me-Arg8-Pro9-D-Ala10-NH2（2）的1H 2D NMR数据，研究了Cα-甲基对促性腺激素释放激素（GnRH）类似物肽构象集合的影响。类似物2的第5和第8位残基中的两个额外Cα-甲基对可观察到的主链NOE强度模式或主链HN质子化学位移没有显著影响，这表明它们不会在肽的构象集合中产生全局变化。在D-Arg8-Pro9的构象中观察到了由取代引起的局部变化。