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超越醌甲烷:从 COS/HS 供体中最小化亲电副产物的最新进展。

Moving Past Quinone-Methides: Recent Advances Toward Minimizing Electrophilic Byproducts from COS/HS Donors.

机构信息

Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology. University of Oregon. Eugene, OR,United States.

出版信息

Curr Top Med Chem. 2021;21(32):2882-2889. doi: 10.2174/1568026621666210622130002.

Abstract

Hydrogen sulfide (HS) is an important biomolecule that plays key signaling and protective roles in different physiological processes. With goals of advancing both the available research tools and the associated therapeutic potential of HS, researchers have developed different methods to deliver HS on demand in different biological contexts. A recent approach to develop such donors has been to design compounds that release carbonyl sulfide (COS), which is quickly converted to HS in biological systems by the ubiquitous enzyme carbonic anhydrase (CA). Although highly diversifiable, many approaches using this general platform release quinone methides or related electrophiles after donor activation. Many such electrophiles are likely scavenged by water, but recent efforts have also expanded alternative approaches that minimize the formation of electrophilic byproducts generated after COS release. This mini-review focuses specifically on recent examples of COS-based HS donors that do no generate quinone methide byproducts after donor activation.

摘要

硫化氢 (HS) 是一种重要的生物分子,在不同的生理过程中发挥着关键的信号转导和保护作用。为了推进 HS 的现有研究工具和相关治疗潜力,研究人员开发了不同的方法,以便在不同的生物环境中按需输送 HS。最近一种开发此类供体的方法是设计释放碳酰硫化物 (COS) 的化合物,在生物系统中,COS 被普遍存在的碳酸酐酶 (CA) 迅速转化为 HS。尽管具有高度的可变性,但许多使用该通用平台的方法在供体激活后会释放出醌亚甲基或相关的亲电试剂。许多此类亲电试剂可能会被水清除,但最近的努力也扩展了替代方法,以最小化 COS 释放后生成的亲电副产物的形成。本综述专门关注最近的 COS 基 HS 供体的例子,这些供体在供体激活后不会生成醌亚甲基副产物。

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