用“剪刀”把分子剪開,，聽起來已經(jīng)夠神奇，但華東理工大學(xué)化學(xué)學(xué)院朱麟勇課題組居然更神：給“剪刀”“上鎖”,，只有某種特殊靶向物質(zhì)“開鎖”后,，“剪刀”才會開剪，分子才會分離,。
這個(gè)名為“靶向激活型光扳機(jī)”的研究成果,，在近期出版的《美國化學(xué)會志》上發(fā)表。該成果將為精確可控地進(jìn)行光激活或釋放來診療疾病及開展生命機(jī)制研究奠定強(qiáng)有力的基礎(chǔ),。
據(jù)朱麟勇教授介紹,，化學(xué)分子中有一些作用類似于“扳機(jī)”的分子基團(tuán)，只要照射某種光,，就會激發(fā)分子基團(tuán)內(nèi)發(fā)生光剪切,，母體分子就會分離，這些分子基團(tuán)由此得名“光扳機(jī)”或“光籠”,。光扳機(jī)近年來備受關(guān)注,，廣泛應(yīng)用于光激活生物信號分子或熒光、光活化DNA或蛋白功能以及光控藥物或基因釋放等方面,。
“但僅僅激發(fā)光剪切效應(yīng)來分離分子是不夠的,，我們的創(chuàng)新之處是讓光剪切的發(fā)生精確可控，形象地說,，就是先給光扳機(jī)‘上鎖’,，只有遇上‘鑰匙’開鎖后，光剪切才會發(fā)生,。”朱麟勇說,。
朱麟勇課題組設(shè)計(jì)的全新概念“靶向激活型光扳機(jī)”，在常規(guī)香豆素光扳機(jī)分子上引入一把“鎖”,，使它失去熒光和光剪切性能,，只有當(dāng)“鎖”被靶向物質(zhì)打開或所在的特定微環(huán)境被破壞時(shí),，失去的性能才能被有效激活和恢復(fù)。“這給疾病靶向治療開辟了新途徑,。例如,，腫瘤部位的生物特征必然和健康部位不同，我們可以據(jù)此做出一把‘鎖’,，用腫瘤特征物質(zhì)作為‘鑰匙’,，這個(gè)帶‘鎖’的物質(zhì)進(jìn)入人體后，只有在腫瘤組織中‘鎖’才被打開,，在光照條件下,，釋放出里面的藥物，選擇性殺死癌細(xì)胞,。”朱麟勇解釋說,。(生物谷：Bioon.com)
doi:10.1021/ja300475k
PMC:
PMID:
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.
