Cation−π Interaction in Model α-Helical Peptides

Zhengshuang Shi, C. Anders Olson, and Neville R. Kallenbach*
Contribution from the Department of Chemistry, New York University, New York 10003
J. Am. Chem. Soc., 2002, 124 (13), pp 3284–3291
DOI: 10.1021/ja0174938
Publication Date (Web): March 12, 2002
Copyright © 2002 American Chemical Society
*

 To whom correspondence should be addressed. Email:  nrk1@nyu.edu. Telephone:  (212) 998-8757. Fax:  (212) 260-7905.

Abstract

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Cation−π interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation−π interaction by determining its effect on the helicity of model peptides using a combination of CD and NMR spectroscopy. The data show that a single Trp/Arg interaction on the surface of a peptide can make a significant net favorable free energy contribution to helix stability if the two residues are positioned with appropriate spacing and orientation. The solvent-exposed Trp→Arg (i, i + 4) interaction in helices can contribute −0.4 kcal/mol to the helix stability, while no free energy gain is detected if the two residues have the reversed orientation, Arg→Trp (i, i + 4). The derived free energy is consistent with other experimental results studied in proteins or model peptides on cation−π interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation−π interaction provides no net free energy to helix stability. Thus the Trp→Arg interaction is stronger than Phe→Arg. The cation−π interactions are not sensitive to the screening effect by adding neutral salt as indicated by salt titration. Our results are in qualitative agreement with theoretical calculations emphasizing that cation−π interactions can contribute significantly to protein stability with the order Trp > Phe. However, our and other experimental values are significantly smaller than estimates from theoretical calculations.

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History

  • Published In Issue April 03, 2002
  • Received November 8, 2001

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