An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis
Name
D4CC00293H.pdf
Size
1.33 MB
Format
Adobe PDF
Checksum (MD5)
7bba72d2b70c75415b10e3fb7bd9448f
Author(s)
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.
Date Issued
March 26, 2024
Journal
ChemComm
Publisher
Royal Society of Chemistry
Citation
Chem. Commun., 2024,60, 4238-4241
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/D4CC00293H
