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Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein
Derek C Church1,2, Elizabathe Davis1,2, Adam A Caparco1
1Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Reports. Physical Science
|February 23, 2023
Summary
New protein-polymer conjugates (PPCs) using polynorbornene offer a promising alternative to PEGylation, reducing immunogenicity while maintaining protein bioactivity for improved therapeutic applications.
Area of Science:
- Bioconjugation Chemistry
- Polymer Science
- Protein Engineering
Background:
- Protein-polymer conjugates (PPCs) enhance protein therapeutics but PEGylation faces limitations due to immunogenicity.
- Pre-existing anti-PEG antibodies can reduce the efficacy of PEGylated protein drugs.
Purpose of the Study:
- To develop novel protein-polymer conjugates (PPCs) as alternatives to PEGylation.
- To synthesize water-soluble polynorbornene (PNB)-based PPCs using a grafting-from ring-opening metathesis polymerization (ROMP) approach.
- To evaluate the bioactivity and immunogenicity of these novel PPCs.
Main Methods:
- Utilized optimized conditions for living aqueous grafting-from ring-opening metathesis polymerization (ROMP).
- Synthesized polynorbornene (PNB)-based protein-polymer conjugates (PPCs) with lysozyme (Lyz-PPCs) and bacteriophage Qβ (Qβ-PPCs).
- Assessed protein bioactivity and immunogenicity, including recognition by anti-PEG antibodies.
Main Results:
- Synthesized Lyz-PPCs retained nearly 100% bioactivity.
- Qβ-PPCs showed up to a 35% decrease in protein immunogenicity compared to controls.
- PNB-based PPCs derived from NB-Zwit demonstrated over 95% reduction in recognition by anti-PEG antibodies, unlike NB-PEG derived PPCs.
Conclusions:
- Developed a novel method for synthesizing protein-polymer conjugates (PPCs) via grafting-from ROMP.
- Demonstrated the potential of PNB-based PPCs as effective alternatives to PEGylation.
- Highlighted the utility of these novel PPCs in evading immune recognition for enhanced biotherapeutic applications.
