A cysteine-triggered fluorogenic donor base on native chemical ligation for tracking H₂S delivery in vivo

A hydrogen sulfide (H₂S) donor is a fundamental molecular tool used as an exogenous source in biological studies and therapies. However, finding a controllable and visual fluorescent H₂S donor is difficult. We report a new H₂S donor, HSD560, the H₂S release of which is triggered by cysteine. Importantly, the H₂S generation is accompanied with enhanced green fluorescence, which could be utilized to track H₂S release in cells using microscopy. H₂S release from HSD560 undergoes a non-enzymatic native chemical ligation (NCL) process, which provides an accurate match with activated fluorescence and localization of H₂S in zebrafish.