PERIODICITY OF POLAR AND NONPOLAR AMINO-ACIDS IS THE MAJOR DETERMINANT OF SECONDARY STRUCTURE IN SELF-ASSEMBLING OLIGOMERIC PEPTIDES

The tendency of a polypeptide chain to form alpha-helical or beta-stra nd secondary structure depends upon local and nonlocal effects. Local effects reflect the intrinsic propensities of the amino acid residues for particular secondary structures, while nonlocal effects reflect th e positioning of the individual residues in the context of the entire amino acid sequence, In particular, the periodicity of polar and nonpo lar residues specifies whether a given sequence is consistent with amp hiphilic alpha-helices or beta-strands, The importance of intrinsic pr opensities was compared to that of polar/nonpolar periodicity by a dir ect competition. Synthetic peptides were designed using residues with intrinsic propensities that favored one or the other type of secondary structure, The polar/nonpolar periodicities of the peptides were desi gned either to be consistent with the secondary structure favored by t he intrinsic propensities of the component residues or in other cases to oppose these intrinsic propensities, Characterization of the synthe tic peptides demonstrated that in all cases the observed secondary str ucture correlates with the periodicity of the peptide sequence-even wh en this secondary structure differs from that predicted from the intri nsic propensities of the component amino acids. The observed secondary structures are concentration dependent, indicating that oligomerizati on of the amphiphilic peptides is responsible for the observed seconda ry structures, Thus, for self-assembling oligomeric peptides, the pola r/nonpolar periodicity can overwhelm the intrinsic propensities of the amino acid residues and serves as the major determinant of peptide se condary structure.