The Structural Characterization of Folded Peptides Containing the Conformationally Constrained beta-Amino Acid Residue beta(2,2)Ac(6)c

Basuroy, Krishnayan and Karuppiah, Vasantham and Shamala, Narayanaswamy and Balaram, Padmanabhan (2012) The Structural Characterization of Folded Peptides Containing the Conformationally Constrained beta-Amino Acid Residue beta(2,2)Ac(6)c. In: HELVETICA CHIMICA ACTA, 95 (12). pp. 2589-2603.

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Abstract

Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to a-amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for beta and ? residues. Five peptides containing the achiral beta 2,2-disubstituted beta-amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid (beta 2,2Ac6c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib-beta 2,2Ac6c-Aib-OMe (1) adopts a novel fold stabilized by two intramolecular H-bonds (C11 and C9) of opposite directionality. The tetrapeptide Boc-Aib-beta 2,2Ac6c]2-OMe (2) and pentapeptide Boc-Aib-beta 2,2Ac6c]2-Aib-OMe (3) form short stretches of a hybrid a beta C11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib-beta 2,2Ac6c-OMe (5) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the beta 2,2Ac6c residue, forming a polar sheet like H-bond. The protected derivative Ac-beta 2,2Ac6c-NHMe (4) adopts a locally folded gauche conformation about the C beta?Ca bonds (?=-55.7 degrees). Of the seven examples of beta 2,2Ac6c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of beta 2,2Ac6c and beta 3,3Ac6c residues, in peptides, is presented. Backbone torsional parameters of H-bonded a beta/beta a turns are derived from the structures presented in this study and earlier reports.

Item Type:	Journal Article
Publication:	HELVETICA CHIMICA ACTA
Publisher:	WILEY-V C H VERLAG GMBH
Additional Information:	Copyright for this article belongs to WILEY-V C H VERLAG GMBH, GERMANY
Keywords:	Amino acids;Peptides;Cyclohexanecarboxylic acid;1-(aminomethyl)-
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Physical & Mathematical Sciences > Physics
Date Deposited:	22 Jan 2013 06:18
Last Modified:	22 Jan 2013 06:18
URI:	http://eprints.iisc.ac.in/id/eprint/45674

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