The unexplored potential of quinone methides in chemical biology.
The unexplored potential of quinone methides in chemical biology.
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DOI：
10.1016/j.bmc.2019.04.001
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发表时间：
2019-06
影响因子：
3.5
通讯作者：
Aisling Minard;Denise Liano;Xiaofan Wang;M. Di Antonio
中科院分区：
文献类型：
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作者：
Aisling Minard;Denise Liano;Xiaofan Wang;M. Di Antonio
醌甲基化物（QMs）是在各种生物相容性条件下可以从稳定的前体有效地产生的瞬时反应性物种。由于它们的亲电性质，QMs已被广泛探索作为DNA和蛋白质在生理条件下的交联剂。然而，QMs也具有二烯特性，并且可以通过Diels-Alder反应与富电子亲二烯体发生不可逆反应。这种特殊的反应性最近已被开发用于在活细胞中用荧光团标记生物分子。QMs的特征在于两个独特的性质，这使它们成为化学生物学应用的理想候选者：i）它们可以通过生物正交协议从非常稳定的前体有效地原位生成ii）它们是可逆的交联剂，使它们适合于“捕获和释放”靶富集实验。然而，迄今为止，在化学-生物学测定开发的背景下，只有很少的实例报告真正利用了QM独特的化学性质。在这篇综述中，我们将研究最相关的例子，说明使用量子力学的化学生物学目的的好处，我们将期待新的方法，以进一步在生物相关的背景下的应用。
Quinone methides (QMs) are transient reactive species that can be efficiently generated from stable precursors under a variety of biocompatible conditions. Due to their electrophilic nature, QMs have been widely explored as cross-linking agents of DNA and proteins under physiological conditions. However, QMs also have a diene character and can irreversibly reactviaDiels-Alder reaction with electron-rich dienophiles. This particular reactivity has been recently exploited to label biomolecules with fluorophores in living cells.QMs are characterised by two unique properties that make them ideal candidates for chemical biology applications: i) they can be efficiently generatedin situfrom very stable precursors by means of bio-orthogonal protocols ii) they are reversible cross-linking agents, making them suitable for “catch and release” target-enrichment experiments. Nevertheless, there are only few examples reported to date that truly take advantage of QMs unique chemistry in the context of chemical-biology assay development. In this review, we will examine the most relevant examples that illustrate the benefit of using QMs for chemical biology purposes and we will anticipate novel approaches to further their applications in biologically relevant contexts.