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Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity

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 be...

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Autores principales: Church, Derek C., Davis, Elizabathe, Caparco, Adam A., Takiguchi, Lauren, Chung, Young Hun, Steinmetz, Nicole F., Pokorski, Jonathan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933924/
https://www.ncbi.nlm.nih.gov/pubmed/36816463
http://dx.doi.org/10.1016/j.xcrp.2022.101067
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author Church, Derek C.
Davis, Elizabathe
Caparco, Adam A.
Takiguchi, Lauren
Chung, Young Hun
Steinmetz, Nicole F.
Pokorski, Jonathan K.
author_facet Church, Derek C.
Davis, Elizabathe
Caparco, Adam A.
Takiguchi, Lauren
Chung, Young Hun
Steinmetz, Nicole F.
Pokorski, Jonathan K.
author_sort Church, Derek C.
collection PubMed
description 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.
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spelling pubmed-99339242023-02-16 Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity Church, Derek C. Davis, Elizabathe Caparco, Adam A. Takiguchi, Lauren Chung, Young Hun Steinmetz, Nicole F. Pokorski, Jonathan K. Cell Rep Phys Sci Article 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. 2022-10-19 2022-09-22 /pmc/articles/PMC9933924/ /pubmed/36816463 http://dx.doi.org/10.1016/j.xcrp.2022.101067 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Church, Derek C.
Davis, Elizabathe
Caparco, Adam A.
Takiguchi, Lauren
Chung, Young Hun
Steinmetz, Nicole F.
Pokorski, Jonathan K.
Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title_full Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title_fullStr Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title_full_unstemmed Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title_short Polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
title_sort polynorbornene-based bioconjugates by aqueous grafting-from ring-opening metathesis polymerization reduce protein immunogenicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933924/
https://www.ncbi.nlm.nih.gov/pubmed/36816463
http://dx.doi.org/10.1016/j.xcrp.2022.101067
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