title: Cation-pi interaction in model alpha-helical peptides.
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.
authors.affiliation: Department of Chemistry, New York University, New York 10003, USA.
authors.forename: Zhengshuang
authors.initials: Z
authors.lastname: Shi
authors.forename: C Anders
authors.initials: CA
authors.lastname: Olson
authors.forename: Neville R
authors.initials: NR
authors.lastname: Kallenbach
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D002412:Cations; D009842:Oligopeptides; D010649:Phenylalanine; D014364:Tryptophan; D001120:Arginine