Trimethyl lock: A trigger for molecular release in chemistry, biology, and pharmacology.
Trimethyl lock: A trigger for molecular release in chemistry, biology, and pharmacology.
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DOI：
10.1039/c2sc20536j
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发表时间：
2012-01-01
期刊：
影响因子：
8.4
通讯作者：
Raines RT
中科院分区：
文献类型：
--
作者：
Levine MN;Raines RT
三甲基锁是一种邻羟基二氢肉桂酸衍生物，其中三个侧甲基之间不利的空间相互作用促进内酯化形成氢香豆素。即使当亲电子试剂是酰胺并且离去基团是小分子药物、荧光团、肽或核酸的氨基时，该反应也非常快。酚羟基的 O-酰化可阻止反应，从而引发反应。因此，氨基从酰胺的释放可以与指定酯的水解相结合（或与再生羟基的另一种化学反应相结合）。三甲基锁缀合物易于合成，使三甲基锁成为化学生物学及相关领域的高度通用的模块。
The trimethyl lock is an o-hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O-Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields.