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Updated: Feb 26, 2026

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
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An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species
Yueqin Zheng1, Bingchen Yu1, Zhen Li2
1Department of Chemistry, Georgia State University, Atlanta, GA, 30303-3083, USA.
Abstract:
A strategy to deliver a well-defined persulfide species in a biological medium is described. Under near physiological conditions, the persulfide prodrug can be activated by an esterase to generate a "hydroxymethyl persulfide" intermediate, which rapidly collapses to form a defined persulfide. Such persulfide prodrugs can be used either as chemical tools to study persulfide chemistry and biology or for future development as H2 S-based therapeutic reagents. Using the persulfide prodrugs developed in this study, the reactivity between S-methyl methanethiosulfonate (MMTS) with persulfide was unambiguously demonstrated. Furthermore, a representative prodrug exhibited potent cardioprotective effects in a murine model of myocardial ischemia-reperfusion (MI/R) injury with a bell shape therapeutic profile.
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