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An Esterase‐Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species
Author(s) -
Zheng Yueqin,
Yu Bingchen,
Li Zhen,
Yuan Zhengnan,
Organ Chelsea L.,
Trivedi Rishi K.,
Wang Siming,
Lefer David J.,
Wang Binghe
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201704117
Subject(s) - prodrug , chemistry , esterase , hydroxymethyl , combinatorial chemistry , stereochemistry , biochemistry , enzyme
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 H 2 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.