Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage.
Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage.
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DOI：
10.1021/jacs.7b11217
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发表时间：
2018-03-14
影响因子：
15
通讯作者：
Weissleder R
中科院分区：
文献类型：
--
作者：
Carlson JCT;Mikula H;Weissleder R
键断裂反应的最新发展已经扩大了生物正交化学的范围，超越了点击连接，并实现了探针激活和治疗递送的新策略。然而，这些应用仍处于起步阶段，需要进一步的创新才能实现体内通用和广泛有用的工具所需的效率。在这些化学反应中，四嗪/反式环辛烯点击释放反应具有示例性动力学和适应性，但仅实现部分释放并且不完全理解，这限制了其应用。研究该反应性能的机械特征，我们发现了深刻的pH敏感性，利用它与酸官能化的四嗪，既增强和显着加速释放，并最终发现了一个意想不到的死端异构体的原因差释放。实施简便的方法来防止形成这种死胡同，我们已经取得了卓越的效率，在整个生理pH范围内基本上完全释放，增强药物递送策略并扩大生物正交开/关控制的动态范围。
Recent developments in bond cleavage reactions have expanded the scope of bioorthogonal chemistry beyond click ligation and enabled new strategies for probe activation and therapeutic delivery. These applications, however, remain in their infancy, with further innovations needed to achieve the efficiency required for versatile and broadly useful tools in vivo. Among these chemistries, the tetrazine/trans-cyclooctene click-to-release reaction has exemplary kinetics and adaptability but achieves only partial release and is incompletely understood, which has limited its application. Investigating the mechanistic features of this reaction’s performance, we discovered profound pH sensitivity, exploited it with acid-functionalized tetrazines that both enhance and markedly accelerate release, and ultimately uncovered an unexpected dead-end isomer as the reason for poor release. Implementing facile methods to prevent formation of this dead end, we have achieved exceptional efficiency, with essentially complete release across the full scope of physiologic pH, potentiating drug-delivery strategies and expanding the dynamic range of bioorthogonal on/off control.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
影响因子：
4.7
作者：
Courtis, Alexandra M.;Santos, Sofia A.;Guan, Yinghua;Hendricks, J. Adam;Ghosh, Balaram;Szantai-Kis, D. Miklos;Reis, Surya A.;Shah, Jagesh V.;Mazitschek, Ralph
通讯作者：
Mazitschek, Ralph
DOI：
10.1039/c0cc03078c
发表时间：
2010-11-14
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Li Z;Cai H;Hassink M;Blackman ML;Brown RC;Conti PS;Fox JM
通讯作者：
Fox JM
影响因子：
3.1
作者：
Emilia Pacheco, Maria;Bruzzone, Liliana
通讯作者：
Bruzzone, Liliana
影响因子：
16.6
作者：
Carlson, Jonathan C. T.;Meimetis, Labros G.;Hilderbrand, Scott A.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph