Abstract
Protein-polymer conjugates (PPCs) improve therapeutic efficacy of proteins and have been widely used for the treatment of various diseases such as cancer, diabetes, and hepatitis. PEGylation is considered as the "gold standard" in bioconjugation, although in practice its clinical applications are becoming limited because of extensive evidence of immunogenicity induced by pre-existing anti-PEG antibodies in patients. Here, optimized reaction conditions for living aqueous grafting-from ring-opening metathesis polymerization (ROMP) are utilized to synthesize water-soluble polynorbornene (PNB)-based PPCs of lysozyme (Lyz-PPCs) and bacteriophage Qβ (Qβ-PPCs) as PEG alternatives. Lyz-PPCs retain nearly 100% bioactivity and Qβ-PPCs exhibit up to 35% decrease in protein immunogenicity. Qβ-PPCs derived from NB-PEG show no reduction in recognition by anti-PEG antibodies while Qβ-PPCs derived from NB-Zwit show >95% reduction as compared with Qβ-PEG. This work demonstrates a new method for PPC synthesis and the utility of grafting from PPCs to evade immune recognition.