Comparison of helix-stabilizing effects of α,α-dialkyl glycines with linear and cycloalkyl side chains

Vijayalakshmi, S. ; Rao, R. Balaji ; Karle, I. L. ; Balaram, P. (2000) Comparison of helix-stabilizing effects of α,α-dialkyl glycines with linear and cycloalkyl side chains Biopolymers, 53 (1). pp. 84-98. ISSN 0006-3525

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Official URL: http://www3.interscience.wiley.com/journal/6900008...

Related URL: http://dx.doi.org/10.1002/(SICI)1097-0282(200001)53:1 <84::AID-BIP8 >3.0.CO;2-W

Abstract

The ability of α,α-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 = -aminoisobutyric acid, Dpg = α,α-di-n-propyl glycine, Deg = α,α-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.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons, Inc.
Keywords:heptapeptides;alpha-helix;310-helix;crystal structures;solution structures;helix transitions;solvent dependency
ID Code:4289
Deposited On:13 Oct 2010 09:55
Last Modified:16 May 2016 14:57

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