There is considerable interest in the site specific conjugation of molecules, i.e. �tags�, to peptides and proteins. These tags may be used for attachment of probes for imaging, for selective purification or detection in complex mixtures, for enhancement of therapeutic properties, or as labels to assist in proteomic analysis. Such modifications typically rely on chemoselective reactions with natural amino acid functional groups, e.g. cysteine thiols, or biosynthetic incorporation of unnatural amino acids that present functionality for bioorthogonal reactivity, e.g. azide groups. While many approaches exist for selective tagging of peptides and proteins, few of these, aside from labile disulfides, are reversible modifications that allow triggered regeneration of the unmodified samples. Tag removal is advantageous for some applications, such as release of therapeutic peptides from a carrier, or release of tagged protein digests from solid supports or affinity columns to allow downstream proteomic analysis. Here, we present the development of reagents for completely reversible, chemoselective alkylation of natural methionine residues in peptides and polypeptides. These reagents have been optimized to give stable sulfonium products, allow secondary modifications, and allow selective tag removal under mild conditions.

Reversible chemoselective tagging and functionalization of methionine containing peptides and polypeptides

246th National Meeting (2013)

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