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

doi:10.1016/j.eurpolymj.2018.07.041

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 journal › Article › peer-review

13 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 language	English
Pages (from-to)	15-24
Number of pages	10
Journal	European Polymer Journal
Volume	107
DOIs	https://doi.org/10.1016/j.eurpolymj.2018.07.041
State	Published - Oct 2018
Externally published	Yes

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.

Funders	Funder number
Neuroscience Institute
National Science Foundation	CHE-1039870, CHE-0130903
Army Research Office	W911NF-17-1-0015, 68271-CH
Carnegie Mellon University
National Science Foundation	CHE-0839233

Keywords

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

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10.1016/j.eurpolymj.2018.07.041

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title = "Grafting strategies for the synthesis of active DNase I polymer biohybrids",

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.",

keywords = "Biohybrids, DNase I, Grafting-from, Grafting-to, Protein polymer hybrids",

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

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2018",

month = oct,

doi = "10.1016/j.eurpolymj.2018.07.041",

language = "אנגלית",

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AU - Cohen-Karni, Devora

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AU - Sloane, Samantha

AU - Daman, Nicholas

AU - Xu, Chen

AU - Guth, Jared

AU - Kenneth Wickiser, J.

AU - Tomycz, Nestor

AU - Page, Richard C.

AU - Konkolewicz, Dominik

AU - Averick, Saadyah

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AB - 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.

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Grafting strategies for the synthesis of active DNase I polymer biohybrids

Abstract

Bibliographical note

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Keywords

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