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

✍ Scribed by S. Vijayalakshmi; R. Balaji Rao; I. L. Karle; P. Balaram

• Publisher: Wiley (John Wiley & Sons)
• Year: 2000
• Tongue: English
• Weight: 272 KB
• Volume: 53
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(200001)53:1<84::aid-bip8>3.0.co;2-w

✦ Synopsis

The ability of ␣,␣-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 ϭ Ac 8 c, Ac 7 c, Aib, Dpg ,and Deg, where Ac 8 c ϭ 1-aminocyclooctane-1-carboxylic acid, Ac 7 c ϭ 1-aminocycloheptane-1-carboxylic acid, Aib ϭ ␣-aminoisobutyric acid, Dpg ϭ ␣,␣-di-n-propyl glycine, Deg ϭ ␣,␣-din-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 ϭ Boc and acetyl). Solution conformations of the five peptides have been studied by 1 H-nmr. In the apolar solvent CDCl 3 , all five peptides favor helical conformations in which the NH groups of residues 3-7 are shielded from the solvent. Successive N i H 7 N iϩ1 H nuclear Overhauser effects over the length of the sequence support a major population of continuous helical conformations. Solvent titration experiments in mixtures of CDCl 3 /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/Ac n c 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 Ac 7 c peptide in DMSO.