An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis
Polymer–protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsol...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Royal Society of Chemistry
2024
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| Online Access: | https://hdl.handle.net/1721.1/156726 |
| _version_ | 1826213527284613120 |
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| author | Liu, Bin Rodriguez, Jacob Kilgallon, Landon J. Wang, Wencong Wang, Yuyan Wang, Aiden Dai, Yutong Nguyen, Hung V.-T. Pentelute, Bradley L. Johnson, Jeremiah A. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Liu, Bin Rodriguez, Jacob Kilgallon, Landon J. Wang, Wencong Wang, Yuyan Wang, Aiden Dai, Yutong Nguyen, Hung V.-T. Pentelute, Bradley L. Johnson, Jeremiah A. |
| author_sort | Liu, Bin |
| collection | MIT |
| description | Polymer–protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by “graft-through” ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP–protein conjugates (albumin and ERG), setting the stage for a new class of BP–protein conjugates for future therapeutic and imaging applications. |
| first_indexed | 2024-09-23T15:50:39Z |
| format | Article |
| id | mit-1721.1/156726 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2025-02-19T04:25:05Z |
| publishDate | 2024 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | mit-1721.1/1567262025-01-12T04:25:31Z An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis Liu, Bin Rodriguez, Jacob Kilgallon, Landon J. Wang, Wencong Wang, Yuyan Wang, Aiden Dai, Yutong Nguyen, Hung V.-T. Pentelute, Bradley L. Johnson, Jeremiah A. Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Polymer–protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by “graft-through” ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP–protein conjugates (albumin and ERG), setting the stage for a new class of BP–protein conjugates for future therapeutic and imaging applications. 2024-09-13T16:16:10Z 2024-09-13T16:16:10Z 2024-03-26 Article http://purl.org/eprint/type/JournalArticle 1364-548X https://hdl.handle.net/1721.1/156726 Chem. Commun., 2024,60, 4238-4241 https://doi.org/10.1039/D4CC00293H ChemComm Creative Commons Attribution-Noncommercial https://creativecommons.org/licenses/by-nc/3.0/ application/pdf Royal Society of Chemistry Royal Society of Chemistry |
| spellingShingle | Liu, Bin Rodriguez, Jacob Kilgallon, Landon J. Wang, Wencong Wang, Yuyan Wang, Aiden Dai, Yutong Nguyen, Hung V.-T. Pentelute, Bradley L. Johnson, Jeremiah A. An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title | An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title_full | An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title_fullStr | An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title_full_unstemmed | An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title_short | An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis |
| title_sort | organometallic swap strategy for bottlebrush polymer protein conjugate synthesis |
| url | https://hdl.handle.net/1721.1/156726 |
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