Selective chemical cleavage of tryptophanyl peptide bonds by oxidative chlorination with N-chlorosuccinimide

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Abstract
Tryptophanyl peptide bonds are selectively cleaved by N-chlorosuccinimide (NCS) under acidic conditions. All other peptide bonds are resistant to cleavage by this reagent. Optimal conditions for cleavage are: 2 equivalents of NCS, pH 4-5, or 50-80% acetic acid for 30 min at room temperature. Under these conditions methionine residues are oxidized to methionine sulfoxides and cysteine to cystine. Other amino acids are not modified. The cleavage reaction was studied with several peptides containing tryptophan residues and yields of cleavage were in the range of 35-45%. The method was successfully applied to several proteins. In .alpha.-lactalbumin, Kunitz trypsin inhibitor and apomyoglobin, selective cleavage of the expected tryptophanyl peptide bonds was obtained in 19-58% yield. The glucagon molecule was fragmented into 2 peptides in 32% yield.