Catalysis in Chemical Modification of Proteins

Abstract Advancement of catalytic transformations in traditional synthetic organic chemistry have made significant impact on development of novel bioconjugation technologies. While a wide range of applications have become possible through catalytic protein bioconjugation approaches, there has been a lack of literature collectively reviewing advances of chemical modification of proteins through the lens of catalysis. This review article is focused on design principles and chemical strategies of nonenzymatic catalysis for targeting natural protein substrates by identifying seven catalysis patterns as organizing topics: electrocatalysis, photocatalysis, metal catalysis, acid catalysis, organocatalysis, supramolecular catalysis, and heterogeneous catalysis. Many literature examples demonstrated possibility of simple translation of small molecule‐based catalysis into protein bioconjugation methodologies, whereas others demonstrated unique approaches such as dual catalytic systems and polypeptide structure‐specific catalysis design. With a series of successful examples, the survey of catalytic approaches for protein bioconjugation also highlighted the remaining challenges and potential future directions of the area of catalytic bioconjugation.