Bioorthogonal chemistry has evolved into a field with broad reaching applications in biology, medicine and materials science. The inverse-electron demand Diels-Alder reaction of s-tetrazines with alkene or alkyne dienophiles, referred to as tetrazine ligation, is a prominent tool in the biorthogonal toolbox. A notable aspect of the tetrazine ligation are the exceptionally high rates of reactivity that can be achieved in simple biomolecular reactions. Scientists at the University of Delaware have developed a new avenue for this reaction wherein biorthogonal reactivity is turned on by a controllable, catalytic stimulus. Either visible light and a long wavelength sensitizer, or very low loadings of horseradish peroxidase are used to catalyze the oxidation of a dihydrotetrazine to a tetrazine. This method can have broad applications in pretargeted drug delivery and photodynamic therapy.
new method represents the first way to 'turn on' the tetrazine ligation using
visible/Near IR light, or through catalysis (enzymatic or unnatural).
process is distinct as the dihydrotetrazine/tetrazine pair used has high
stability towards both oxygen and water.
- This process eliminates the background chemistry, thus making the drug delivery process safer.