EVALUATION OF TICL4-MEDIATED REDUCTION OF METHIONINE SULFOXIDE IN PEPTIDES WITH OXIDIZABLE OR REDUCIBLE RESIDUES

Reduction of methionine sulfoxide with TiCl4/NaI is very rapid for sim ple methionine-containing peptides. The utility of this oxido/reductio n system has been evaluated for three model peptides that contain oxid ation/reduction-sensitive components such as a disulfide bond and/or a tryptophan residue. Completely specific reduction of methionine sulfo xide without some reduction of the the disulfide bond was not possible with TiCl4/NaI. Reduction of the methionine sulfoxide residue in thes e model peptides yielded the desired product as the major component (y ield ca. 70%) when a reaction time of four minutes was used Methionine sulfoxide appears to be the most readily reducible species by low val ent titanium. The competing side reactions observed were disulfide bon d reduction by low valent titanium and/or tryptophan oxidation by the I-2 generated by reduction of the TiCl4 with NaI. These side reactions became a serious problem when longer reaction times were used. The le vels of contaminants generated by these side reactions were observed t o increase with time, reducing the yield of the desired product.