An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species
作者:Yueqin Zheng、Bingchen Yu、Zhen Li、Zhengnan Yuan、Chelsea L. Organ、Rishi K. Trivedi、Siming Wang、David J. Lefer、Binghe Wang
DOI:10.1002/anie.201704117
日期:2017.9.18
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
描述了在生物介质中递送明确定义的过硫化物物种的策略。在接近生理条件的情况下,过硫化物前药可以被酯酶活化以生成“羟甲基过硫化物”中间体,该中间体迅速塌陷以形成确定的过硫化物。此类过硫化物前药既可以用作研究过硫化物化学和生物学的化学工具,也可以作为基于H 2 S的治疗剂用于未来的开发。使用本研究开发的过硫化物前药,S之间的反应性明确证明了带有过硫化物的甲硫基甲基磺酸甲酯(MMTS)。此外,代表性的前药在具有钟形治疗特征的心肌缺血-再灌注(MI / R)损伤的小鼠模型中表现出强力的心脏保护作用。