用“剪刀”把分子剪开，听起来已经够神奇，但华东理工大学化学学院朱麟勇课题组居然更神：给“剪刀”“上锁”，只有某种特殊靶向物质“开锁”后，“剪刀”才会开剪，分子才会分离。
这个名为“靶向激活型光扳机”的研究成果，在近期出版的《美国化学会志》上发表。该成果将为精确可控地进行光激活或释放来诊疗疾病及开展生命机制研究奠定强有力的基础。
据朱麟勇教授介绍，化学分子中有一些作用类似于“扳机”的分子基团，只要照射某种光，就会激发分子基团内发生光剪切，母体分子就会分离，这些分子基团由此得名“光扳机”或“光笼”。光扳机近年来备受关注，广泛应用于光激活生物信号分子或荧光、光活化DNA或蛋白功能以及光控药物或基因释放等方面。
“但仅仅激发光剪切效应来分离分子是不够的，我们的创新之处是让光剪切的发生精确可控，形象地说，就是先给光扳机‘上锁’，只有遇上‘钥匙’开锁后，光剪切才会发生。”朱麟勇说。
朱麟勇课题组设计的全新概念“靶向激活型光扳机”，在常规香豆素光扳机分子上引入一把“锁”，使它失去荧光和光剪切性能，只有当“锁”被靶向物质打开或所在的特定微环境被破坏时，失去的性能才能被有效激活和恢复。“这给疾病靶向治疗开辟了新途径。例如，肿瘤部位的生物特征必然和健康部位不同，我们可以据此做出一把‘锁’，用肿瘤特征物质作为‘钥匙’，这个带‘锁’的物质进入人体后，只有在肿瘤组织中‘锁’才被打开，在光照条件下，释放出里面的药物，选择性杀死癌细胞。”朱麟勇解释说。(生物谷：Bioon.com)
doi:10.1021/ja300475k
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Target-Activated Coumarin Phototriggers Specifically Switch on Fluorescence and Photocleavage upon Bonding to Thiol-Bearing Protein
Qiuning Lin, Chunyan Bao, Shuiyu Cheng, Yunlong Yang, Wei Ji, and Linyong Zhu
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.
