Tyrosine-based bioconjugations : strain-promoted cycloadditions for site-specific generation of protein conjugates

Antibodies are proteins that can specifically target cells and can be tweaked to target the cell of choice, for example cancer cells. When these antibodies are administered, they will target the cancer cells and accumulate near that area. When these antibodies are combined with chemotherapies, they form so called antibody-drug conjugates (ADCs). These compounds have the advantage over regular chemotherapies that the majority will target the cancer cells, resulting in significantly reduced side-effects.

This thesis describes new methods to prepare such compounds. By exposing tyrosine residues via a short peptide tag (GGGGY), they become prone to selective enzymatic oxidation by the enzyme mushroom tyrosinase. The generated intermediate is very reactive to strained alkynes and alkenes, and will react quickly to form stable conjugate. This allows for the easy generation of antibody-drug conjugates, as well as a great variety of other pharmaceutically relevant compounds.