Optimisation of Enzymatic Protein Labelling

Protein conjugation is an essential technology across biopharma and academic research. In addition to in vitro applications, such as the manufacture of conjugate vaccines and antibody-drug conjugates, methods can be applied within the cell or on the cell surface. Chemical protein conjugation techniques often result in heterogeneous mixtures and require extensive optimisation. In contrast, labelling using transpeptidases, such as sortase, results in single homogeneous products. However, these reactions are limited by reversibility and hydrolysis, which necessitates further optimisation to achieve full conversion.

This project developed novel strategies to rapidly optimise protein labelling with the overarching goal of quantitative labelling using little to no excess of substrate. The developed labelling strategy achieves high yields while significantly reducing the required amount of substrate and has many potential applications, as highlighted above.