Related Experiment Video
Updated: Jan 12, 2026
Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
Cyclometalated Gold(III)-Mediated Cysteine Arylation: A Bioorthogonal Platform for Covalent Targeting of
Udara Munugoda1, Sean T Gilpatrick1, Debarati Das1
1Department of Chemistry, University of Kentucky, Lexington, Kentucky, 40506, USA.
None:
Intrinsically disordered proteins (IDPs) remain largely inaccessible to covalent chemical tools due to their structural plasticity and lack of defined pockets. We introduce a bioorthogonal cyclometalated gold(III) platform of monodentate phosphine-supported AuP1-8 complexes that selectively and irreversibly arylate cysteine residues via enhanced Lewis acidity. This platform enables targeting of low-reactivity, buried, or dynamically disordered cysteines across the human proteome. Chemoproteomic, structural, and computational analyses establish an expanded ligandable cysteinome, including transiently helical LLCLL motifs in intrinsically disordered regions (IDRs). Our findings establish a new class of metal-mediated bioorthogonal reagents for proteome-wide cysteine labeling, functional interrogation of disordered proteins, and future therapeutic and diagnostic applications.
