Influence of N-Methylation on a Cation−π Interaction Produces a Remarkably Stable β-Hairpin Peptide

Robert M. Hughes and Marcey L. Waters*
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290
J. Am. Chem. Soc., 2005, 127 (18), pp 6518–6519
DOI: 10.1021/ja0507259
Publication Date (Web): April 13, 2005
Copyright © 2005 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, marcey@unc.edu

Abstract

Abstract Image

The methylation of lysine in histone tails is a common posttranslational modification that functions in histone-regulated chromatin condensation, with binding of methylated lysine occurring in aromatic pockets on chromodomain proteins. We have synthesized a highly stable 12-residue β-hairpin peptide that exploits the histone-related cation−π interaction between a methylated lysine residue and a tryptophan residue. Thermodynamic analysis reveals significant entropic stabilization of the peptide due to methylation of the lysine residue. Chemical denaturation of the peptide demonstrates two-state behavior. In comparison to other reported, highly stable designed β-hairpins, this peptide is the most thermally stable β-hairpin reported to date. This study provides insight into the role of Lys methylation in histone proteins and more generally in mediating protein−protein interactions.

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History

  • Published In Issue May 11, 2005
  • Received February 3, 2005

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