Grafting strategies for the synthesis of active DNase I polymer biohybrids

Marina Kovaliov, Devora Cohen-Karni, Kevin A. Burridge, Dorian Mambelli, Samantha Sloane, Nicholas Daman, Chen Xu, Jared Guth, J. Kenneth Wickiser, Nestor Tomycz, Richard C. Page, Dominik Konkolewicz, Saadyah Averick

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Protein polymer hybrids play an increasingly important role in therapeutics and biocatalysis. Synthesis of these biohybrids can be achieved by either the grafting-from or grafting-to strategy and are generally thought to be interchangeable. Therefore, when choosing between these two strategies the decision is usually based on polymer accessibility and purification preference. However, in this study, we demonstrated that the choice of the polymer ligation strategy played a significant role in the stability and bioactivity of the final hybrid. Our goal was to prepare a thermally stable DNase I polymer hybrid by utilizing either synthetic strategies. We found that the grafting-from strategy using reversible addition-fragmentation chain transfer polymerization (RAFT) or atom transfer radical polymerization (ATRP) yielded DNase I biohybrids with no activity. Control reactions were used to demonstrate inherent protein deactivation caused by the grafting-from conditions for either ATRP or RAFT polymerization. The grafting-to method yielded active and thermally stable DNase I biohybrids.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalEuropean Polymer Journal
Volume107
DOIs
StatePublished - Oct 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Ltd

Funding

We gratefully acknowledge The Army Research Office (Award# 68271-CH ) Young Investigator Program ( W911NF-17-1-0015 ) and the Neuroscience Institute at AHN for funding NMR measurements and instrumentation at CMU which was partially supported by NSF ( CHE-0130903 and CHE-1039870 ). The MALDI-TOF data were collected using instrumentation purchased with NSF grant award CHE-0839233 . We gratefully acknowledge The Army Research Office (Award# 68271-CH) Young Investigator Program (W911NF-17-1-0015) and the Neuroscience Institute at AHN for funding NMR measurements and instrumentation at CMU which was partially supported by NSF (CHE-0130903 and CHE-1039870). The MALDI-TOF data were collected using instrumentation purchased with NSF grant award CHE-0839233.

FundersFunder number
Neuroscience Institute
National Science FoundationCHE-1039870, CHE-0130903
Army Research OfficeW911NF-17-1-0015, 68271-CH
Carnegie Mellon University
National Science FoundationCHE-0839233

    Keywords

    • Biohybrids
    • DNase I
    • Grafting-from
    • Grafting-to
    • Protein polymer hybrids

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