title: Unusually stable helix formation in short alanine-based peptides.
abstract: Short, 16-residue, alanine-based peptides show stable alpha-helix formation in H2O. This result is surprising when contrasted with the classical view that regards the alpha-helix as a marginally stable structure in H2O and considers short helices unstable. The alanine-based peptides are solubilized by insertion of three or more residues of a single charge type, lysine (+) or glutamic acid (-). The results cannot be explained by helix stabilization resulting from concentration-dependent association or by the interaction of charged residues with the helix dipole. Our results are not predicted by the parameters for alanine and lysine that have been determined by the "host-guest" method: these parameters predict that a 16-residue peptide should not show measurable alpha-helix formation. Analysis of the role of the hydrophobic interaction in alpha-helix formation [Richards, F.M. & Richmond, T. (1978) in Molecular Interactions and Activity in Proteins, Ciba Foundation Symposium 60, ed. Wolstenholme, G.E. (Excepta Medica Amsterdam), pp. 23-25] does not show an unusually strong hydrophobic interaction in a helical block of alanine residues. The likely explanation for our results is, therefore, that individual alanine residues have a high helical potential. It is not yet known whether any other amino acids show this property, and the origin of this property is also unknown.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, CA 94305.
authors.forename: S
authors.initials: S
authors.lastname: Marqusee
authors.forename: V H
authors.initials: VH
authors.lastname: Robbins
authors.forename: R L
authors.initials: RL
authors.lastname: Baldwin
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D007700:Kinetics; D010455:Peptides / Q000138:chemical synthesis; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D010455:Peptides; D000409:Alanine