Poly(oxanorbornene)-Protein Conjugates Prepared by Grafting-to Romp as Alternatives for Peg.

PEGylation is the gold standard in protein-polymer conjugation, improving circulation half-life of biologics while mitigating the immune response to a foreign substance. However, pre-existing anti-PEG antibodies in healthy humans are becoming increasingly prevalent and elicitation of anti-PEG antibodies when patients are administered with PEGylated therapeutics challenges their safety profile. In our current study, two distinct amine-reactive poly(oxanorbornene) (PONB) imide-based water-soluble block co-polymers were synthesized using ring opening metathesis polymerization (ROMP). The synthesized block-copolymers include PEG-based PONB-PEG and sulfobetaine-based PONB-Zwit. The polymers were then covalently conjugated to amine residues of lysozyme (Lyz) and urate oxidase (UO) using a grafting-to bioconjugation technique. Both Lyz-PONB and UO-PONB conjugates retained significant bioactivities after bioconjugation. Immune recognition studies of UO-PONB conjugates indicated comparable lowering of protein immunogenicity when compared to PEGylated UO. PEG-specific immune recognition was negligible for UO-PONB-Zwit conjugates, as expected. These polymers provide a new alternative for PEG-based systems that retain high levels of activity for the biologic while showing improved immune recognition profiles. This article is protected by copyright. All rights reserved.