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Cation-pi interaction in model alpha-helical peptides.

Zhengshuang Shi·C Anders Olson·Neville R Kallenbach
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Abstract

Cation-pi interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation-pi 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-pi interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation-pi interaction provides no net free energy to helix stability. Thus the Trp-->Arg interaction is stronger than Phe-->Arg. The cation-pi 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-pi 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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Amino Acid SequenceArginineCationsCircular DichroismMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularOligopeptidesPhenylalanineProtein Structure, SecondaryThermodynamicsTryptophanJournal Article

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Zhengshuang Shi, C Anders Olson, Neville R Kallenbach. 2002-04-03. Cation-pi interaction in model alpha-helical peptides.. https://doi.org/10.1021/ja0174938

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