FSK hydrochloride is fluorosulfonyloxybenzoyl-L-lysine, which features a long, flexible aryl fluorosulfate-containing side chain that can reach protein sites inaccessible to covalent conjugation. FSK hydrochloride modifies nanomolecules to target epidermal growth factor receptor ( EGFR ), resulting in irreversibly bound covalent interactions. Through genetically encoded chemical crosslinking, FSK hydrochloride captures unknown enzyme-substrate interactions in living cells, targets residues other than Cys, and mediates crosslinking at the binding periphery. FSK hydrochloride enables the construction of a bioreactive SuFEx system for generating covalent bonds in various proteins both in vitro and in vivo.
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