A chemoselective, convenient, and mild synthetic strategy to modify peptides on a cysteine sulfhydryl group is described. It simply requires activated molecular sieves to selectively promote S-alkylation in the presence of peptide nucleophilic functionalities. The procedure is easy to perform, fast, and provides high yields even in the case of poor electrophilic groups. Moreover, the method allows an efficient one-pot poly alkylation, proving that the sulfhydryl reactivity does not rely on its specific position within the peptide sequence. 2013 American Chemical Society

*** IBB - CNR ***

Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, United States

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