Yang Yang, Liu Xiaoyang, Wu Xiaofeng, Liang Gaolin
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou, Nanjing 210096, China.
Chem Biomed Imaging. 2023 Dec 31;2(2):98-116. doi: 10.1021/cbmi.3c00117. eCollection 2024 Feb 26.
With high efficiency, mild conditions, and rapid reaction rate, click reactions have garnered much attention in the field of bioimaging since proposed by Sharpless et al. in 2001 (Angew. Chem., Int. Ed.2001, 40, 2004-2021). Inspired by the regenerative pathway of d-luciferin in fireflies, Liang et al. (Nat. Chem.2010, 2, 54-60) raised a 2-cyanobenzothiazole (CBT)-cysteine (Cys) click condensation reaction in 2010, which exhibits a higher second-order reaction rate (9.19 M s) and superior biocompatibility. As it has been developed in the past decade, remarkable progress has been made in the construction of enzyme-instructed CBT-Cys-based bioimaging probes. This review introduces the concept of the CBT-Cys click reaction, elucidates the mechanism of the CBT-Cys click reaction, and concerns the development progress of CBT-Cys reaction and its derived reactions [i.e., 2-cyano-6-hydroxyquinoline (CHQ)-Cys reaction and 2-pyrimidinecarbonitrile (PMN)-Cys reaction]. Furthermore, we give a comprehensive and up-to-date review of enzyme-instructed CBT-Cys-like click reaction-based probes with significantly enhanced imaging signal and contrast for various bioimaging modes, including fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and positron emission tomography. In the end, we discuss the possible challenges and opportunities that may arise in the future.
自2001年被夏普莱斯等人提出以来（《德国应用化学》，国际版，2001年，第40卷，第2004 - 2021页），点击反应因其高效、温和的条件和快速的反应速率，在生物成像领域备受关注。受萤火虫中d - 荧光素再生途径的启发，梁等人（《自然·化学》，2010年，第2卷，第54 - 60页）于2010年提出了2 - 氰基苯并噻唑（CBT）- 半胱氨酸（Cys）点击缩合反应，该反应具有更高的二级反应速率（9.19 M⁻¹s⁻¹）和优异的生物相容性。在过去十年的发展中，基于酶引导的CBT - Cys生物成像探针的构建取得了显著进展。本综述介绍了CBT - Cys点击反应的概念，阐明了CBT - Cys点击反应的机制，并关注了CBT - Cys反应及其衍生反应[即2 - 氰基 - 6 - 羟基喹啉（CHQ）- Cys反应和2 - 嘧啶甲腈（PMN）- Cys反应]的发展进程。此外，我们对基于酶引导的类似CBT - Cys点击反应的探针进行了全面且最新的综述，这些探针在各种生物成像模式（包括荧光成像、光声成像、磁共振成像和正电子发射断层扫描）中具有显著增强的成像信号和对比度。最后，我们讨论了未来可能出现的挑战和机遇。
