$\alpha,\beta$hybrid peptides:a polypeptide helix with a central segment containing two consecutive $\beta$-amino acid residues

Roy, Rituparna S and Karle, Isabella L and Raghothama, S and Balaram, P (2004) $\alpha,\beta$hybrid peptides:a polypeptide helix with a central segment containing two consecutive $\beta$-amino acid residues. In: Proceedings of the National Academy of Sciences, 101 (47). pp. 16478-16482.

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Abstract

Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl (Boc)-Val-Ala-Phe-$\alpha$-aminoisobutyric acid (Aib)-(R)-$\beta^3$- homovaline ($\beta$Val)-(S)-$\beta^3$-homophenylalanine ($\beta$Phe)-Aib-Val-Ala- Phe-Aib-methyl ester (OMe) (peptide 1; $\beta$Val and $\beta$Phe are $\beta$amino acids generated by homologation of the corresponding L-residues) establish that insertion of two consecutive $\beta$ residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2–10 of peptide 1. At the site of insertion of the $\beta\beta$ segment, helical hydrogen-bonded rings are expanded. A $C_1_5$ hydrogen bond for the $\alpha\beta\beta$segment and two $C_1_4$ hydrogen bonds for the $\alpha\alpha\beta$or $\beta\alpha\alpha$ segments have been characterized. The following conformational angles were determined from the crystal structure for the $\beta$ residues: $\beta$ Val-5 ($\phi = -126 ^o $,$\theta = 76 ^o $ , and $\psi = -124$) and $\beta$Phe-6 ($\phi = - 88^o,$ $\theta = 80^o,$ and $\psi = - 118$). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz $^1H-NMR$ studies establish a continuous helix over the entire length of the peptide in $CDCl_3$ solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.

Item Type:	Journal Article
Publication:	Proceedings of the National Academy of Sciences
Publisher:	National Academy of Sciences.
Additional Information:	The copyright of this article belongs to National Academy of Sciences.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	03 Apr 2006
Last Modified:	19 Sep 2010 04:24
URI:	http://eprints.iisc.ac.in/id/eprint/5913

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