Evaluation of TiCl4-mediated reduction of methionine sulfoxide in peptides with oxidizable or reducible residues.

Abstract

Reduction of methionine sulfoxide with TiCl4/NaI is very rapid for simple methionine-containing peptides. The utility of this oxido/reduction system has been evaluated for three model peptides that contain oxidation/reduction-sensitive components such as a disulfide bond and/or a tryptophan residue. Completely specific reduction of methionine sulfoxide without some reduction of the disulfide bond was not possible with TiCl4/NaI. Reduction of the methionine sulfoxide residue in these model peptides yielded the desired product as the major component (yield ca. 70%) when a reaction time of four minutes was used. Methionine sulfoxide appears to be the most readily reducible species by low valent titanium. The competing side reactions observed were disulfide bond reduction by low valent titanium and/or tryptophan oxidation by the I2 generated by reduction of the TiCl4 with NaI. These side reactions became a serious problem when longer reaction times were used. The levels of contaminants generated by these side reactions were observed to increase with time, reducing the yield of the desired product.