Rapid, stable, chemoselective labeling of thiols with Julia-Kocieński-like reagents: a serum-stable alternative to maleimide-based protein conjugation.

Proteins modified with fluorescent or biologically active agents are powerful reagents in chemistry, biology, and medicine. [1] Selectivity for certain of the natural 20 amino acids in the presence of many unprotected amino acid residues is necessary for the selective modification of proteins. [2] The development of bioconjugation reactions has largely focused on the modification of lysine and cysteine side chains. Conjugation to cysteine, which is a rare amino acid and often exists as a disulfide pair in native proteins, can be readily achieved as a consequence of the relatively low pKa value and potent nucleophilicity of the thiolate anion. [3] Significant research efforts have been made to identify reagents that enable blocking or labeling of protein thiols with high selectivity and conversion yields. [4] Among those,