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Conformational Choices for the Stereochemically Constrained gamma-Amino Acid Residue Gabapentin: Theoretical Studies and Correlation With Experimental Results

Vasudev, Prema G and Chatterjee, Sunanda and Ramakrishnan, Chandrasekharan and Shamala, Narayanaswamy and Balaram, Padmanabhan (2009) Conformational Choices for the Stereochemically Constrained gamma-Amino Acid Residue Gabapentin: Theoretical Studies and Correlation With Experimental Results. In: Biopolymers, 92 (5). pp. 426-435.

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Official URL: http://www3.interscience.wiley.com/journal/1223434...

Abstract

Gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn) is an achiral, conformationally constrained gamma amino acid residue. A survey of available crystal structures of Gpn peptides reveals that the torsion angles about the C-gamma-C-beta (theta(1)) and C-beta-C-alpha(theta(2)) bonds are overwhelmingly limited to gauche, gauche (g(+)g(+)/g(-)g(-)) conformations. The Gpn residue forms C-7 and C-9 hydrogen bonds in which the donor and acceptor atoms come from the flanking peptide units. In combination with alpha amino acid residues alpha gamma and gamma alpha segments can adopt C-12 hydrogen bonded structures. The conformational choices available to the Gpn residue have been probed using energy calculations, adopting a grid search strategy. Ramachandran phi-psi maps have been constructed for fixed values of theta(1) and theta(2), corresponding to the gauche and trans conformations. The sterically allowed and energetically favorable regions of conformational space have been defined and experimental observations compared. C-7 and C-9 hydrogen bonded conformational families have been identified using a grid search approach in which theta(1) and theta(2) values are varied over a range of +/- 10 degrees about ideal values at 1 degrees intervals. The theoretical analysis together with experimental observations for 59 Gpn residues from 35 crystal structures permits definition of the limited range of conformational possibilities at this gamma amino acid residue. .

Item Type: Journal Article
Additional Information: Copyright of this article belongs to John Wiley & Sons.
Keywords: gabapentin; gamma-amino acid; conformational analysis; grid search; hydrogen bonds
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 29 Oct 2009 06:09
Last Modified: 19 Sep 2010 05:50
URI: http://eprints.iisc.ernet.in/id/eprint/24554

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