ROLE OF HYDROPHOBIC INTERACTIONS AND DESOLVATION IN DETERMINING THE STRUCTURAL-PROPERTIES OF A MODEL ALPHA-BETA PEPTIDE

Model AB, a 20-amino acid peptide that was designed to adopt an alpha beta tertiary structure stabilized by hydrophobic interactions between residues in adjacent helical and extended segments, exhibited large p K(a) shifts of several ionizable groups and slow hydrogen/deuterium ex change rates of nearly all the peptide amide groups [Butcher, D. J., B ruch, M, D. & Moe, G, T, (1995) Biopolymers 36, 109-120]. These proper ties, which depend on structure and hydration, are commonly observed i n larger proteins but are quite unusual for small peptides, To identif y which of several possible features of the peptide design are most im portant in determining these properties, several closely related analo gs of Model AB were characterized by CD and NMR spectroscopy, The resu lts show that hydrophobic interactions between adjacent helical and ex tended segments are structure-determining and have the additional effe ct of altering water-peptide interactions over much of the peptide sur face. These results may have important implications for understanding mechanisms of protein folding and for the design of independently fold ing peptides.