De novo Design of $\Delta F$ -containing Heme-binding Peptides

Rai, Jagdish and Raghothama, S and Sahal, D (2007) De novo Design of $\Delta F$ -containing Heme-binding Peptides. In: Chemical Biology & Drug Design, 69 (2). pp. 119-123.

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Abstract

The structural characterization of de novo designed metalloproteins together with determination of chemical reactivity can provide a detailed understanding of the relationship between protein structure and functional properties. Toward this goal, using the basic scaffold of 1pbz (Rosenblatt et al. (2003) Proc Natl Acad Sci U S A;100:13140) we have designed cyclic $\Delta F$-containing heme-binding peptides. The $\alpha$- and $\beta$-bands in UV–Vis spectroscopy are indicative of bis-His-ligated heme complex. Most of our $\Delta F$-containing peptides have more affinity to cobalt(III)Coproporphyrinate-I than heme because cobalt(III)Coproporphyrinate-I contains two additional propionate groups which can have salt bridge interactions with the lysine residues in the peptide. Helicity induction in peptide by $\Delta F$ and aromatic interaction of $\Delta F$ with heme have increased the heme affinity of CP-6-12pbz (cyclic peptide with substitutions of Ala at positions 6 and 12 by $\Delta F$; 905/mM) compared with 1pbz (279/mM). The nuclear magnetic resonance spectra are indicative of overall helical structure for CP-6-12pbz and CP-6-12pbz in complex with cobalt (III)Coproporphyrinate-I. The descending order of heme affinity in peptides (CP-6-12pbz > CP-12pbz > CP-5-12pbz) indicates that $\Delta F$ at i + 3 or i - 3 from the central H9 favors heme binding but disrupts the same when placed at i - 4.

Item Type:	Journal Article
Publication:	Chemical Biology & Drug Design
Publisher:	Blackwell Synergy
Additional Information:	Copyright of this article belongs to Blackwell Synergy. The author is in NMR research Center.
Keywords:	DF (a,b-dehydro-phenyl-alanine);cyclic peptide;designed peptide;helical conformations;heme-binding peptide;heme proteins;soret band
Department/Centre:	Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	04 Jun 2008
Last Modified:	19 Sep 2010 04:45
URI:	http://eprints.iisc.ac.in/id/eprint/14159

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