Abstract
Determining small molecule—target protein interaction is essential for the chemical proteomics. One of the most important keys to explore biological system in chemical proteomics field is finding first-class molecular tools. Chemical probes can provide great spatiotemporal control to elucidate biological functions of proteins as well as for interrogating biological pathways. The invention of bioorthogonal chemistry has revolutionized the field of chemical biology by providing superior chemical tools and has been widely used for investigating the dynamics and function of biomolecules in live condition. Among 20 different bioorthogonal reactions, tetrazine ligation has been spotlighted as the most advanced bioorthogonal chemistry because of their extremely faster kinetics and higher specificity than others. Therefore, tetrazine ligation has a tremendous potential to enhance the proteomic research. This review highlights the current status of tetrazine ligation reaction as a molecular tool for the chemical proteomics.
Highlights
Chemical proteomics has become essential for drug discovery and development [1]
Bioorthogonal chemistry has revolutionized the field of chemical biology by providing powerful chemical tools including metabolite analogous tracking, activity-based protein profiling, targetguided synthesis of enzyme inhibitors, and imaging small molecules in living cells/animals [6,7,8]
Tetrazine (Tz) ligation has recently emerged as a valuable bioorthogonal coupling tool because of its fast kinetics, spontaneous reactivity without catalysts, and high reaction yield in aqueous solution [8]
Summary
Chemical proteomics has become essential for drug discovery and development [1]. Chemical proteomics utilizes chemical probes to understand biological functions of proteins, inform small molecule-protein interactions [2] and validate new druggable protein targets [3]. Tetrazine fluorophores can generally serve as a fluorogenic probe during the iEDDA reaction (Fig. 3). Initial demonstrations of tetrazine ligation as a bioconjugation method for fluorescent imaging of protein were independently reported from two different research groups in 2008 [36, 37]. Imaging binding partners of a small molecule in live cells was feasible with the tetrazine ligation reaction (Scheme 1).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
