Biorthogonal release reactions based on benzonorbornadiene derivatives that are highly stable and release cargo molecules for use in drug delivery systems.

Biorthogonal dissociative reactions boast diverse potential applications in chemical biology and drug delivery. Specific cargo molecules within cells are released when benzonorbornadienes react with tetrazines to release amines from carbamate leaving groups. These carrier molecules are highly stable at physiological conditions, but react rapidly with tetrazines and near-quantitatively release cargo molecules such as drugs and optical reporters. The reactions are designed to take place without interfering with the existing cell chemistry and could serve a number of different purposes including DNA sequencing, cell imaging, drug delivery systems, and reaction protection groups.

Proof of Concept

• Allows use in cells, tissue samples, and in vivo.
• Increases reaction rate.
• Facilitates complete release of cargo molecules.
• Eliminates need for metal catalyst.
• Reduces toxicity.

Xu M, Tu J, Franzini R. (2017). Rapid and efficient tetrazine-induced drug release from highly stable benzonorbornadiene derivatives. Chemical Communications. 53:6271-6274. doi: 10.1039/C7CC03477

Xu M, Galindo-Murillo R, Cheatham TE, & Franzini R (2017). Dissociative reactions of benzonorbornadienes with tetrazines: scope of leaving groups and mechanistic insights. Organic & Biomolecular Chemistry. 15(46): 9855-9865. doi: 10.1039/c7ob02191g.

Publication Number: US-2019-0300539-A1
Patent Title: Benzonorbornadiene Deriviatives and Reactions Thereof
Jurisdiction/Country: United States
Application Type: Non-Provisional

Jason Young
(801) 587-0519
jason.r.young@utah.edu