A variety of bioorthogonal chemical tools have been developed and widely used in the study of biological phenomena in situ. Tetrazine bioorthogonal chemistry exhibits ultrafast reaction kinetics, excellent biocompatibility, and precise optical regulatory capabilities. Fluorogenic tetrazine bioorthogonal probes have achieved particularly diverse applications in bioimaging and disease diagnosis and treatment. This Viewpoint briefly introduces the characteristics and advantages of tetrazine bioorthogonal chemistry, some design strategies of fluorogenic tetrazine probes, and the status of applications of these tools to in vivo imaging, as well as disease diagnosis and treatment. Finally, we discuss challenges and propose future trends in the field of fluorogenic tetrazine probes. This Viewpoint offers insights into the development of new bioorthogonal tools for chemical biology research and for the design of new drugs.
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http://dx.doi.org/10.1021/cbmi.4c00095 | DOI Listing |
Chem Biomed Imaging
January 2025
Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging and Functional and Molecular lmaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University. Chengdu 610041, Sichuan, China.
A variety of bioorthogonal chemical tools have been developed and widely used in the study of biological phenomena in situ. Tetrazine bioorthogonal chemistry exhibits ultrafast reaction kinetics, excellent biocompatibility, and precise optical regulatory capabilities. Fluorogenic tetrazine bioorthogonal probes have achieved particularly diverse applications in bioimaging and disease diagnosis and treatment.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Laboratory of Medicinal Chemical Biology, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, China.
Bioorthogonalized light-responsive click-and-uncage platform has enabled precise cell surface engineering and timed payload release, but most of such photoactivatable prodrugs have "always-on" photoactivity leading to the dark toxicity. On the other hand, the conditionally activatable photocage is limited to the application of fluorogenic probe/photosensitizer liberation. Herein, we devise a conditionally activatable theranostic platform based on the tetrazine (Tz)-boron-dipyrromethene (BODIPY) construct, in which tetrazine serves as a quencher motif to disable both the fluorescence and photoresponsivity of BODIPY.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
Department of Chemistry, Seoul National University, Seoul, 08826, Korea.
Methods Mol Biol
November 2024
State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biomedical Sciences, Hunan University, Changsha, China.
Accurate evaluation of the tumor-related mRNA expression levels provides important information for cancer diagnosis and therapy. We recently reported a fluorogenic sensor by coupling tetrazine-mediated bioorthogonal reaction with catalytic hairpin assembly for precise imaging of GalNac-T mRNA in live cells. Fluorescence signals are specifically generated by target mRNA triggered spatial localization of bioorthogonal chemicals.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo nám. 2, 16000, Prague 6, Czech Republic.
Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine-mediated cleavage of trans-cyclooctene caged compounds (click-to-release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans-cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo-tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pK).
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