Stereochemically Constrained Peptides. Theoretical and Experimental Studies on the Conformations of Peptides Containing 1-Aminocyclohexanecarboxylic Acid

Paul, PKC and Sukumar, M and Bardi, R and Piazzesi, AM and Valle, G and Toniolo, C and BaIaram, P (1986) Stereochemically Constrained Peptides. Theoretical and Experimental Studies on the Conformations of Peptides Containing 1-Aminocyclohexanecarboxylic Acid. In: Journal of the American Chemical Society, 108 (20). pp. 6363-6370.

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Abstract

Conformational energy calculations on the model system N-acetyl- 1 -aminocyclohexanecarboxylic acid N'methylamide $(Ac-Acc^6-NHMe)$, using an average geometry derived from 13 crystallographic observations, establish that the $Acc^6$ residue is constrained to adopt conformations in the $3_{10}/\alpha$-helical regions of \o \psi space $(\o = \pm 50 \pm 20^0$ , $\psi = \pm 50 \pm 20^0)$. In contrast, the \alpha, \alpha -dialkylated residue with linear hydrocarbon side chains, \alpha, \alpha-di-n-propylglycine favors fully extended backbone structures $(\o \approx \psi \approx = 180^0)$. The crystal structures of two model peptides, Boc-($Acc^6)_3$-OMe (type III \beta -turn at $-Acc^6(1)-Acc^6(2)-)$ and Boc-Pro-$Acc^6$-Ala-OMe (type II \beta -turn at -Pro-$Acc^6$-), establish that $Acc^6$ residues can occupy either position of type III \beta turns and the i + 2 position of type II \beta -turns. The stereochemical rigidity of these peptides is demonstrated in solution by NMR studies, which establish the presence of one intramolecular hydrogen bond in each peptide in $CDCl_3$, and $(CD_3)_2SO$. Nuclear Overhauser effects permit characterization of the \beta -turn conformations in solution and establish their similarity to the solid-state structures. The implications for the use of $Acc^6$ residues in conformational design are considered.

Item Type:	Journal Article
Publication:	Journal of the American Chemical Society
Publisher:	American Chemical Society
Additional Information:	Copyright of this article belongs to American Chemical Society.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	11 Jul 2008
Last Modified:	19 Sep 2010 04:47
URI:	http://eprints.iisc.ac.in/id/eprint/14919

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