Protection of methionine in peptides during iodination by sulfonium salt formation

A method for the prevention of methionine oxidation during iodination of tyrosine containing peptides is reported. The methionine containing peptide is converted into the corresponding S-tert.-butylsulfonium derivative, which is iodinated using iodine monochloride. After removal of the S-tert.-butyl group and purification, sulfoxide-free 3,5 diiodotyrosine (Dit) peptides were obtained. Dit8-substance P, Dit8-physalaemin 6-11 and Dit1, Met5-enkephalin were synthesized by this route. Tritium labeling of Dit1, Met5-enkephalin yielded 3H-enkephalin with a specific radioactivity of 38 Ci/mmol.