Poly(Oxanorbornene)-Protein Conjugates Prepared by Grafting-to ROMP as Alternatives for PEG.

Autor:	Davis E; Department of NanoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA., Caparco AA; Department of NanoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA., Steinmetz NF; Department of NanoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA.; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA.; Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Radiology, University of California, San Diego, La Jolla, CA, 92093, USA.; Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA., Pokorski JK; Department of NanoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA.; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA.; Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, CA, 92093, USA.
Jazyk:	angličtina
Zdroj:	Macromolecular bioscience [Macromol Biosci] 2024 Feb; Vol. 24 (2), pp. e2300255. Date of Electronic Publication: 2023 Sep 26.
DOI:	10.1002/mabi.202300255
Abstrakt:	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, preexisting 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 the current study, two distinct amine-reactive poly(oxanorbornene) (PONB) imide-based water-soluble block co-polymers are synthesized using ring-opening metathesis polymerization (ROMP). The synthesized block-copolymers include PEG-based PONB-PEG and sulfobetaine-based PONB-Zwit. The polymers are 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 a comparable lowering of protein immunogenicity when compared to PEGylated UO. PEG-specific immune recognition is 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. (© 2023 Wiley-VCH GmbH.)
Databáze:	MEDLINE
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