Tetrazole Photoclick Chemistry: Reinvestigating Its Suitability as a Bioorthogonal Reaction and Potential Applications

The bioorthogonality of tetrazole photoclick chemistry has been reassessed. Upon photolysis of a tetrazole, the highly reactive nitrile imine formed undergoes rapid nucleophilic reaction with a variety of nucleophiles present in a biological system, along with the expected cycloaddition with alkenes...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2016-02, Vol.55 (6), p.2002-2006
Main Authors: Li, Zhengqiu, Qian, Linghui, Li, Lin, Bernhammer, Jan C., Huynh, Han Vinh, Lee, Jun-Seok, Yao, Shao Q.
Format: Article
Language:English
Subjects:
affinity-based probes
Alkenes
bioorthogonality
Biosensing Techniques
Biosensors
Chemistry
Click Chemistry
Crosslinking
Cycloaddition
Dyes
Fluorescence
Fluorescent Dyes - chemistry
Hep G2 Cells
Humans
Imaging
Mammalian cells
Mammals
Molecular Structure
Nucleophiles
photo-crosslinking
Photochemical Processes
Photolysis
Probes
Protein Kinases - analysis
Protein Kinases - metabolism
Staurosporine
Tetrazoles
Tetrazoles - chemistry
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Summary:The bioorthogonality of tetrazole photoclick chemistry has been reassessed. Upon photolysis of a tetrazole, the highly reactive nitrile imine formed undergoes rapid nucleophilic reaction with a variety of nucleophiles present in a biological system, along with the expected cycloaddition with alkenes. The alternative use of the tetrazole photoclick reaction was thus explored: tetrazoles were incorporated into Bodipy and Acedan dyes, providing novel photo‐crosslinkers with one‐ and two‐photon fluorescence Turn‐ON properties that may be developed into protein‐detecting biosensors. Further introduction of these photo‐activatable, fluorogenic moieties into staurosporine resulted in the corresponding probes capable of photoinduced, no‐wash imaging of endogenous kinase activities in live mammalian cells. “Tie” and “see”: By reassessing the bioorthogonality of tetrazole photoclick chemistry, an alternative use of tetrazoles in chemical biology is proposed, as general photo‐crosslinkers with potential fluorescence Turn‐ON properties. This method could be used to develop affinity‐based probes for live‐cell imaging of endogenous kinase activities. WH=warhead.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201508104