title: Contribution of aromatic interactions to alpha-helix stability.
abstract: The influence of natural and unnatural i, i + 4 aromatic side chain-side chain interactions on alpha-helix stability was determined in Ala-Lys host peptides by circular dichroism (CD). All interactions investigated provided some stability to the helix; however, phenylalanine-phenylalanine (F-F) and phenylalanine-pentafluorophenylalanine (F-f5F) interactions resulted in the greatest enhancement in helicity, doubling the helical content over i, i + 5 control peptides at internal positions. Quantification of these interactions using AGADIR multistate helix-coil algorithm revealed that the F-F and F-f5F interaction energies are equivalent at internal positions in the sequence (deltaGF-F = deltaGF-f5F = -0.27 kcal/mol), despite the differences in their expected geometries. As the strength of a face-to-face stacked phenyl-pentafluorophenyl interaction should surpass an edge-to-face or offset-stacked phenyl-phenyl interaction, we believe this result reflects the inability of the side chains in F-f5F to attain a fully stacked geometry within the context of an alpha-helix. Positioning the interactions at the C-terminus led to much stronger interactions (deltaGF-F = -0.8 kcal/mol; deltaGF-f5F = -0.55 kcal/mol) likely because of favorable chi(1) rotameric preferences for aromatic residues at C-capping regions of alpha-helices, suggesting that aromatic side chain-side chain interactions are an effective alpha-helix C-capping method.
authors.affiliation: Department of Chemistry, UNC Chapel Hill, Venable and Kenan Laboratories, CB 3290, Chapel Hill, North Carolina 27599, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Butterfield
authors.forename: Paresma R
authors.initials: PR
authors.lastname: Patel
authors.forename: Marcey L
authors.initials: ML
authors.lastname: Waters
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D010649:Phenylalanine; D008239:Lysine; D000409:Alanine