Antibody Drug Conjugates (ADCs) are a new class of promising new anti-cancer therapeutics. An ADC comprises a highly cytotoxic compound coupled to a tumour-binding antibody. In this project, we aim to design new ADCs with superior efficacy.
To study the coupling of cytotoxic compounds to proteins, C-terminal conjugation to proteins via tyrosine residues was achieved using mushroom tyrosinase (m-tyrosinase) as oxidative enzyme. A G4Y-tag was introduced to the exposed C-terminus of laminarinase A (LamA) from Pyrococcus furiosus. The newly introduced C-terminal tyrosine was then converted into a 1,2-quinone with m-tyrosinase. C-terminal labelling of LamA was achieved by strain-promoted [4+2] cycloaddition of the 1,2-quinone to a labelled bicyclononyne (BCN).