An Esterase‐Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species

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 p...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-09, Vol.56 (39), p.11749-11753
Main Authors: Zheng, Yueqin, Yu, Bingchen, Li, Zhen, Yuan, Zhengnan, Organ, Chelsea L., Trivedi, Rishi K., Wang, Siming, Lefer, David J., Wang, Binghe
Format: Article
Language:English
Subjects:
Animal models
bell shape therapeutic profile
Chemical compounds
Drugs
Esterase
Hydrogen sulfide
Ischemia
Myocardial ischemia
persulfide
Prodrugs
Reagents
Reperfusion
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Summary: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 H2S‐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. A strategy to deliver a well‐defined persulfide species in a biological medium is described. Under near physiological conditions, a persulfide prodrug is activated by an esterase to generate a hydroxymethyl persulfide intermediate, which rapidly collapses to form a persulfide. Such prodrugs can be used to study persulfide chemistry and biology or for development as H2S‐based therapeutic reagents.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201704117