Catalytic Serine Labeling in Nonaqueous, Acidic Media.

Chemoselective modification of alkylalcohols (e.g., serine residues) on proteins has been a daunting challenge especially in aqueous media. Herein, we report chemical modifications of alkylalcohols in protein and cell lysate samples using carboxylic acid-based bioconjugation media. The acidic medium is not only useful to suppress reactivity of other nucleophiles in proteins, but the medium also serves as a potentially biomolecule-compatible solvent. The acid-catalyzed acylation strategy has a unique selectivity paradigm compared to the common active-serine-targeted method and would act as a new strategy for studying biological roles of serine residues.