Solid State and Solution Conformations of a Hybrid $\alpha \gamma \alpha \alpha \gamma \alpha$ Hexapeptide. Characterization of a Backbone Expanded Analog of the $\alpha$-Polypeptide $3_{(10)}$-Helix

Chatterjee, Sunanda and Vasudev, Prema G and Raghothama, Srinivasarao and Shamala, Narayanaswamy and Balaram, Padmanabhan (2008) Solid State and Solution Conformations of a Hybrid $\alpha \gamma \alpha \alpha \gamma \alpha$ Hexapeptide. Characterization of a Backbone Expanded Analog of the $\alpha$-Polypeptide $3_{(10)}$-Helix. In: Biopolymers, 90 (6). pp. 759-771.

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Abstract

The stereochemically constrained gamma amino acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alpha gamma alpha alpha gamma alpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4\rightarrow 1 C{12} hydrogen bonds across the alpha gamma/gamma alpha segments and one C-10 hydrogen bond across the central alpha alpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl3 solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH - Leu (4) NH and Gpn (2) NH <-> Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs tire presented, both of which contain three hydrogen bonds and ore consistent with the known stereochemical preferences of the Gpn residue.

Item Type:	Journal Article
Publication:	Biopolymers
Publisher:	John Wiley and Sons
Additional Information:	Copyright of this article belongs to John Wiley and Sons.
Keywords:	alpha gamma hybrid peptides;gabapentin peptides;C-12-helix; NMR averaging;solution conformations.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility) Division of Physical & Mathematical Sciences > Physics
Date Deposited:	04 Nov 2009 10:14
Last Modified:	19 Sep 2010 04:58
URI:	http://eprints.iisc.ac.in/id/eprint/17855

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