Invention:
This method is for a novel dual-functional tetrazine reagent with application in Cys-specific bioconjugation and functionalization of target proteins. This class of compounds can be utilized for specific single-thiol targeting. This novel method possesses an electron withdrawing tetrazine substituted vinyl moiety that exists as a Michael receptor for selective conjugation with cysteine and a site for click with trans-cyclooctene (TCO) derivatives to introduce functionality.
Background:
Bioconjugates are molecules with altered chemical structures via substrates or reagents that allows for biomolecule linkage. The most common types of bioconjugation include coupling of a small molecule (such as biotin or a fluorescent dye) to a protein, including arguably the most common type, Antibody Drug Conjugates. These reactions encounter limitations within the ability to achieve conjugation and functionalization simultaneously.
Applications:
- Bioconjugation and functionalization of target proteins in single thiols
- Cellular protein labeling
- Bioorthothogonal chemistry
- Biomedical research
Advantages:
- Selectively activates and delivers the TCO-caged toxic substances to cancer cells
- Reduced side effects of targeted cancer therapy
- Therapeutically significant Cys-specific protein bioconjugation and functionalization
