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 struc ture preferences in the aggregated state (J. Am. Chem. Sec. 1993, 115, 12609). Redox-induced secondary structure changes in the 18-residue p eptide 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-st rand conformation. Here we present a detailed characterization of the third oxidation state of this peptide, in which the methionine residue s are oxidized to the sulfone state. The sulfone form behaves similarl y to the sulfoxide form, even though the sulfone group is somewhat les s hydrophilic than the sulfoxide group. These results provide support for the concept that the conformational preferences of peptides and pr oteins are strongly dependent upon the linear ordering of hydrophilic and lipophilic residues (''amphiphilic order'').