Redox-triggered secondary structure changes in the aggregated states of a designed methionine-rich peptide

We have previously shown that methionine can be used as a ''switchable'' residue for the design of peptides with alternative secondary structure preferences in the aggregated state (J. Am. Chem. Sec. 1993, 115, 12609). Redox-induced secondary structure changes in the 18-residue peptide Ac-YLKAMLEAMAKLMAKLMA-NH2 result from conversion of lipophilic methionine (M) to hydrophilic methionine sulfoxide (M degrees), which transforms a peptide capable of adopting an amphiphilic alpha-helical conformation into a peptide capable of adopting an amphiphilic beta-strand conformation. Here we present a detailed characterization of the third oxidation state of this peptide, in which the methionine residues are oxidized to the sulfone state. The sulfone form behaves similarly to the sulfoxide form, even though the sulfone group is somewhat less hydrophilic than the sulfoxide group. These results provide support for the concept that the conformational preferences of peptides and proteins are strongly dependent upon the linear ordering of hydrophilic and lipophilic residues (''amphiphilic order'').