6 - Protein Conjugation

Summary

This chapter deals with protein bioconjugation, which has emerged as an attractive technique to enhance therapeutic properties of protein-based drugs (e.g. in-vivo circulation, potency). The first part of this chapter aims at answering questions regarding the coupling chemistry and the modelling of the kinetics of bioconjugation. Then, the purification of conjugated proteins is addressed. In particular, chromatography is presented as a technique to purify conjugated proteins according to their extent of conjugation on the one hand and to the position of the conjugated groups on the other hand. Moreover, continuous technologies for both the conjugation reaction and the purification by chromatography are discussed. Finally, the potential benefits from the integration between the reaction and the purification steps in bioconjugation processes are examined. This chapter combines theoretical aspects, model simulations and experimental results from practical examples, for instance dealing with PEGylated proteins and antibody-drug conjugates.