biostudies-literatureUnknown16(42)Lee JThe chemical roles of lanthanides in biology are increasingly recognized, yet remain largely unexplored. Unlike most lanthanides, cerium is redox-active and readily adapted for chemical transformation. Herein, we report a cerium-mediated oxidative thiol-ene coupling between cysteine-derived thiols and styrenes under aqueous conditions, yielding β-hydroxysulfide products. Building on this reactivity, we developed a site-selective cysteine modification strategy using a 17-amino acid cerium-binding sequence. Only cysteines optimally positioned near the vacant coordination site undergo efficient and rapid labeling, particularly with electron-deficient styrene derivatives. This work demonstrates cerium-mediated biological activity and highlights its potential as a reactive center for site-selective bioconjugation and broader biochemical and synthetic applications.Chemical science19658-19668https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486149biostudies-literatureCerium-mediated site-selective cysteine functionalization.PMC12486149Song WJLee JfalseCerium-mediated site-selective cysteine functionalization.The chemical roles of lanthanides in biology are increasingly recognized, yet remain largely unexplored. Unlike most lanthanides, cerium is redox-active and readily adapted for chemical transformation. Herein, we report a cerium-mediated oxidative thiol-ene coupling between cysteine-derived thiols and styrenes under aqueous conditions, yielding β-hydroxysulfide products. Building on this reactivity, we developed a site-selective cysteine modification strategy using a 17-amino acid cerium-binding sequence. Only cysteines optimally positioned near the vacant coordination site undergo efficient and rapid labeling, particularly with electron-deficient styrene derivatives. This work demonstrates cerium-mediated biological activity and highlights its potential as a reactive center for site-selective bioconjugation and broader biochemical and synthetic applications.2025-01-01T00:00:00Z2025 Oct2026-06-05T09:21:48.502Z2026-05-15T03:12:49.934ZS-EPMC124861494104112410.1039/d5sc04538j