An elegant example of how tetrazine ligation can be used in treating desease

The So called Strain-Promoted Inverse Electron-demand Diels-Alder Cycloaddition or SPIEDAC is happen to be the most efficient way to couple molecules in the the chemically complex milieu of cells or biological fluids. This type of reaction that can be efficiently occurred in bioenvironment is called a 'click chemistry' and lately has been used in a number of synthetic biology tasks. 

This time, group of scientists from Eindhoven, Netherlands under the supervision of Marc S. Robillard from Phillips Healthcare elegantly exploited the fast reaction of Tetrazine/Trans-cyclooctene coupling to release the drug locally.

Many of the pharmaceutically active compounds have side effects and for sure many of them are toxic, but sometimes we have no choice and urged to use them. For instance, this happens when somebody is diagnosed with a cancer. Ideally, we want to bring the toxic compound to cancer cell while leaving the rest of the body unaffected. This could be done if something will bring the active chemical to the target where it will act. Quite often this vehicle is an antibody.

Essentially, this group coupled specific antibody to the transcyclooctene that in turn is covalently linked to the cancer treating drug (doxorubicine) via labile carbamate bond. So, the cancer cell-specific antibody will bring the drug to the surface of the cell. Next, we want to release it on place. For this reason we inject tetrazine to the bloodstream that will react with trans-cyclooctene breaking the carbamate bond and releasing the drug locally. This work so far has been done in the tube, so we are looking forward to see on in vivo models. Good luck!