Reactions of I,I-Diacetoxyiodobenzene with Proteins: Conversion of Amide Side-Chains to Amines

Abstract

Experiments with the N-benzyloxycarbonyl derivatives of asparagine and glutamine as models show that, in unbuffered solutions, I,I-diacetoxyiodobenzene (1) is more effective than the corresponding trifluoroacetoxy derivative (2) for converting the amide side-chains of proteins to amines. Maximum modification of the glutamine residues of insulin and lysozyme occurs within 1-2 h of treatment with 1 in aqueous methyl cyanide at 20°C, but asparagine residues react more slowly. The amide side-chains are converted to the corresponding amines in at least 90 % yield, as shown by analysis of acid hydrolysates for aspartic acid, lX,p-diaminopropionic acid, glutamic acid and lX,y-diaminobutyric acid. Numerous side-reactions also occur, tyrosine, cystine, methionine, arginine, lysine and N-terminal residues all being modified to some extent.