Protein PEPylation: A New Paradigm of Protein-Polymer Conjugation.

Various polymers have been tested for protein conjugation with a goal of bridging the complementary advantages of both components. However, many of these polymers, including the most well-established PEG, are nondegradable, which raises potential concerns on their cumulative chronic toxicity. Moreover, the immunogenicity of PEG has recently evoked considerable controversy. Synthetic polypeptides, on the other hand, are biomimetic polymers with tunable degradability, versatile side chain functionalities, unique secondary structures, and fascinating self-assembly behaviors. These properties have made them promising materials in protein modification for various applications. In this Topical Review, we summarize recent advances and list a number of interesting future directions in protein-polypeptide conjugation, which we termed protein PEPylation.