Stereochemistry of linking segments in the design of helix–helix motifs in peptides. Crystallographic comparison of a glycyl–dipropylglycyl–glycyl segment in a tripeptide and a 14-residue peptide

Datta, Saumen and Kaul, Ramesh and Rao, Balaji R and Shamala, N and Balaram, P (1997) Stereochemistry of linking segments in the design of helix–helix motifs in peptides. Crystallographic comparison of a glycyl–dipropylglycyl–glycyl segment in a tripeptide and a 14-residue peptide. In: Journal of Chemical Society, Perkin Transactions 2 (9). pp. 1659-1664.

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Abstract

As part of a program to develop synthetic helix–linker–helix peptides the conformational properties of various linking segments are currently being investigated. The propensity of alpha, alpha-di-n-propylglycine (Dpg) residues to adopt backbone conformations in the extended region of the Ramachandran map, suggested by theoretical calculations and supported by experimental observations, prompted us to investigate the utility of the Gly-Dpg-Gly segment as a rigid linking motif. The crystal structure of the achiral tripeptide Boc-Gly-Dpg-Gly-OH 1 revealed a fully extended conformation (phi = ±178, psi = ±171) at Dpg(2), with Gly(1) adopting a helical conformation (phi = -+72, psi = -+328). The addition of flanking helical segments in the 14 residue peptide Boc-Val-Val-Ala-Leu-Gly-Dpg-Gly-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe 2 resulted in the crystallographic characterization of a continuous helix over the entire length of the peptide. Peptide 1 crystallized in the centrosymmetric space group P21/c with a = 9.505(2) Å, b = 11.025(2) Å, c = 20.075(4) Å, ‚ = 90.198 and Z = 4. Peptide 2 crystallized in space group P212121 with a = 10.172(1) Å, b = 17.521(4) Å, c = 46.438(12) Å and Z = 4. A comparative analysis of Gly-Dpg-Gly segments from available crystal structures indicates a high conformational variability of this segment. This analysis suggests that context and environment may be strong conformational determinants for the Gly-Dpg-Gly segment.

Item Type:	Journal Article
Publication:	Journal of Chemical Society, Perkin Transactions 2
Publisher:	Royal Society of Chemistry
Additional Information:	Copyright for this article belongs to the Royal Society of Chemistry.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Physical & Mathematical Sciences > Physics
Date Deposited:	26 Oct 2004
Last Modified:	19 Sep 2010 04:16
URI:	http://eprints.iisc.ac.in/id/eprint/2196

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