Shanghai Key Laboratory of Functional Materials Chemistry, Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, PR China.
J Am Chem Soc. 2012 Mar 21;134(11):5052-5. doi: 10.1021/ja300475k. Epub 2012 Mar 8.
A new concept in which only the molecular target, such as a thiol-bearing protein, can activate the phototrigger has been demonstrated. Such target-activatable phototriggers comprise three parts: a 7-aminocoumarin phototrigger, an electron acceptor (maleimide) that efficiently quenches the coumarin excited state, and a caged leaving group attached to the coumarin. In the absence of mercaptans, photoinduced electron transfer between coumarin and maleimide effectively blocks both the fluorescence and photocleavage pathways. Thiol-bearing molecules, however, readily annihilate the electron acceptor and thus restore the phototrigger for photorelease of the caged cargo (e.g., biotin). Unlike traditional phototriggers, functional-group-activated phototriggers allow easy handling under ambient light, report specific bonding to the target, and enable photocleavage capability selectively at the binding site in situ, thus effectively positioning the photoreleased cargo at the target. Meanwhile, the unique feature of thiol-specific activation of the fluorescence and photocleavage make our new phototrigger a universal tool that can be used to identify accurately protein cysteine S-nitrosylation, a physiologically important posttranslational modification.
已经证明了一种新的概念，其中只有分子靶标，如含有巯基的蛋白质，可以激活光触发。这种靶标激活的光触发包含三个部分：7-氨基香豆素光触发剂、有效猝灭香豆素激发态的电子受体（马来酰亚胺），以及连接到香豆素上的被笼蔽的离去基团。在没有巯基的情况下，香豆素和马来酰亚胺之间的光诱导电子转移有效地阻止了荧光和光裂解途径。然而，含有巯基的分子很容易消除电子受体，从而恢复光触发剂，以释放被笼蔽的货物（例如生物素）。与传统的光触发剂不同，功能基团激活的光触发剂允许在环境光下轻松处理，报告与靶标的特定结合，并在原位选择性地在结合部位实现光裂解能力，从而有效地将光释放的货物定位在靶标上。同时，巯基特异性激活荧光和光裂解的独特特性使我们的新光触发剂成为一种通用工具，可用于准确识别蛋白质半胱氨酸 S-亚硝基化，这是一种生理上重要的翻译后修饰。
