Reagent enables new protein modification

Abstract

Chemists modify protein sidechains to modulate the biomolecules’ functions. Researchers are usually stuck modifying cysteines because the amino acid’s sulfide side chain makes it the most reactive amino acid. But cysteines are relatively rare, representing ~1.9% of the amino acids in human proteins. Cysteines can be installed using genetic engineering, but researchers would like to modify fully functional native proteins. An international team of researchers led by Goncalo J. L. Bernardes of the University of Cambridge and the Institute of Molecular Medicine Lisbon and Gonzalo Jimenez-Oses of the University of Rioja has now discovered a sulfonyl acrylate reagent that should give researchers more options for modifying proteins. The reagent selectively targets only the most reactive lysine in a protein—not other lysines or buried cysteines (J. Am. Chem. Soc. 2018, DOI: 10.1021/jacs.7b12874). Lysines are nucleophilic and much more abundant than cysteines, representing ~5.9% of the amino acids in human protei...