Vijayalakshmi S, Rao R B, Karle I L, Balaram P
Department of Chemistry, Banaras Hindu University, Varanasi, India.
Biopolymers. 2000 Jan;53(1):84-98. doi: 10.1002/(SICI)1097-0282(200001)53:1<84::AID-BIP8>3.0.CO;2-W.
The ability of alpha, alpha-di-n-alkyl glycines with linear and cyclic alkyl side chains to stabilize helical conformations has been compared using a model heptapeptide sequence. The conformations of five synthetic heptapeptides (Boc-Val-Ala-Leu-Xxx-Val-Ala-Leu-OMe, Xxx = Ac8c, Ac7c, Aib, Dpg, and Deg, where Ac8c = 1-aminocyclooctane-1-carboxylic acid, Ac7c = 1-aminocycloheptane-1-carboxylic acid, Aib = alpha-aminoisobutyric acid, Dpg = alpha,alpha-di-n-propyl glycine, Deg = alpha,alpha-di-n-ethyl glycine) have been investigated. In crystals, helical conformations have been demonstrated by x-ray crystallography for the peptides, R-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe, (R = Boc and acetyl). Solution conformations of the five peptides have been studied by 1H-nmr. In the apolar solvent CDCl3, all five peptides favor helical conformations in which the NH groups of residues 3-7 are shielded from the solvent. Successive NiH<-->Ni + 1H nuclear Overhauser effects over the length of the sequence support a major population of continuous helical conformations. Solvent titration experiments in mixtures of CDCl3/DMSO provide evidence for solvent-dependent conformational transitions that are more pronounced for the Deg and Dpg peptides. Solvent-dependent chemical shift variations and temperature coefficients in DMSO suggest that the conformational distributions in the Deg/Dpg peptides are distinctly different from the Aib/Acnc peptides in a strongly solvating medium. Nuclear Overhauser effects provide additional evidence for the population of extended backbone conformations in the Dpg peptide, while a significant residual population of helical conformations is still detectable in the isomeric Ac7c peptide in DMSO.
使用一个七肽模型序列，比较了具有直链和环状烷基侧链的α,α-二正烷基甘氨酸稳定螺旋构象的能力。研究了五种合成七肽（Boc-Val-Ala-Leu-Xxx-Val-Ala-Leu-OMe，Xxx = Ac8c、Ac7c、Aib、Dpg和Deg，其中Ac8c = 1-氨基环辛烷-1-羧酸，Ac7c = 1-氨基环庚烷-1-羧酸，Aib = α-氨基异丁酸，Dpg = α,α-二正丙基甘氨酸，Deg = α,α-二正乙基甘氨酸）的构象。在晶体中，通过X射线晶体学证明了肽R-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe（R = Boc和乙酰基）的螺旋构象。通过1H-核磁共振研究了这五种肽的溶液构象。在非极性溶剂CDCl3中，所有五种肽都倾向于形成螺旋构象，其中残基3-7的NH基团被溶剂屏蔽。序列长度上连续的NiH<-->Ni + 1H核Overhauser效应支持了主要的连续螺旋构象群体。CDCl3/DMSO混合物中的溶剂滴定实验提供了溶剂依赖性构象转变的证据，这在Deg和Dpg肽中更为明显。DMSO中溶剂依赖性化学位移变化和温度系数表明，在强溶剂化介质中，Deg/Dpg肽的构象分布与Aib/Acnc肽明显不同。核Overhauser效应为Dpg肽中伸展主链构象的群体提供了额外证据，而在DMSO中的异构体Ac7c肽中仍可检测到大量残留的螺旋构象。
