Peptide Models of Electrostatic Interactions in Proteins: $NMR$ Studies on Two \beta - Turn Tetrapeptides Containing $Asp-His$ and $Asp-Lys$ Salt Bridges

Sahal, Dinkar and Balaram, P (1986) Peptide Models of Electrostatic Interactions in Proteins: $NMR$ Studies on Two \beta - Turn Tetrapeptides Containing $Asp-His$ and $Asp-Lys$ Salt Bridges. In: Biochemistry, 25 (20). pp. 6004-6013.

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Abstract

Two model peptides Boc-Asp-Pro-Aib-X-NHMe [X = His (1) and X = Lys (2)] were synthesized to simulate intramolecular electrostatic interactions between ionizable side chains. Conformational analysis by 270-MHz $^1H NMR$ in $(CD_3)_2 SO$ reveals that the backbone secondary structures of these two peptides are stabilized by two strong intramolecular hydrogen bonds, involving the consecutive carboxy-terminal NH groups. $^1H$ NMR chemical shifts were measured in 1, 2, and a protected derivative, $Boc-Asp(OBz1)$ - Pro-Aib-His-NHMe (3). These shifts were also measured for the model compounds Ac-Lys-NHMe, Boc-Asp-NMMe, and Boc-His-NMe in their different states of ionization. An analysis of the chemical shifts of the ionization-sensitive reporter resonances suggests the formation of a strong intramolecular salt bridge in the lysyl peptide 2 and a bridge of moderate strength in the histidyl peptide 1. A comparison of the temperature dependence of chemical shifts in peptides 1-3 suggests that intramolecular salt bridge formation results in diminished backbone flexibility. The results establish that proximity effects confer far greater stability to intramolecular ion pair interactions vis-a-vis their intermolecular counterparts. The salt bridge interaction in peptide 1 displays a remarkable sensitivity to the dielectric constant of the solvent medium. The results suggest that these peptides are good simulators of the role of salt bridges in the structural dynamics of proteins.

Item Type:	Journal Article
Publication:	Biochemistry
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:	10 Jul 2008
Last Modified:	19 Sep 2010 04:46
URI:	http://eprints.iisc.ac.in/id/eprint/14708

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