Enzymatic approaches to new protein conjugates

Abstract Until recently, polymer–protein PEGylation has for the most part been characterized by chemical approaches to conjugation, and, in fact, the majority of conjugates approved for human use are based on these protocols. The growing demand for site-selective conjugates in which the polymer chain is linked to a single, specific position on the protein sequence has become the driving force for the development of new products. Although some chemical methods meeting the site-selection criteria have been devised, their flexibility in terms of potential sites on the protein for the conjugation process and the number of techniques that are possible continue to be limited. Researchers have turned to enzymatic conjugation approaches to face this crossroad. Enzymes have long been used for protein labeling given their unique properties of specificity and in the light of their catalytic action under physiological conditions. In the footsteps of the promising applications of transglutaminase and sialyltransferase that have already been developed, ever greater numbers of enzymes are being used as tools to mediate polymer conjugation. This chapter will offer an overview of protein–polymer conjugation based on enzyme-catalyzed reactions.