Electron‐Deficient Alkynes as Cleavable Reagents for the Modification of Cysteine‐Containing Peptides in Aqueous Medium

Enriched cleavage : An efficient chemoselective cysteine modification of unprotected peptides and proteins has been developed by using electron‐deficient alkynes in aqueous media. Interestingly, terminal alkynone‐modified peptides could be converted back into the unmodified peptides by cleavage by adding thiols under mild conditions (see scheme). magnified image An efficient method has been developed for the chemoselective cysteine modification of unprotected peptides and proteins in aqueous media through the formation of a vinyl sulfide linkage by using electron‐deficient alkynes, including alkynoic amides, esters and alkynones. The terminal alkynone‐modified peptides could be converted back into the unmodified peptides (81 % isolated yield) by adding thiols under mild conditions. The usefulness of this thiol‐assisted cleavage of the vinyl sulfide linkage in peptides has been exemplified by the enrichment of a cysteine‐containing peptide (71 % recovery) from a mixture of cysteine‐containing and non‐cysteine‐containing peptides.