“Graft-to” Protein/Polymer Conjugates Using Polynorbornene Block Copolymers

Abstract

A series of water-soluble polynorbornene block copolymers prepared via Ring-Opening Metathesis Polymerization (ROMP) were grafted to proteins to form ROMP-derived bioconjugates. ROMP afforded low-dispersity polymers and allowed for strict control over polymer molecular weight and architecture. The polymers consisted of a large block of PEGylated monoester norbornene and were capped with a short block of norbornene dicarboxylic anhydride. This cap served as a reactive linker that facilitated attachment of the polymer to lysine residues under mildly alkaline conditions. The generality of this approach was shown by synthesizing multivalent polynorbornene-modified viral nanoparticles derived from bacteriophage Qβ, a protein nanoparticle used extensively for nanomedicine. The conjugated nanoparticles showed no cytotoxicity to NIH 3T3 murine fibroblast cells. These findings establish protein bioconjugation with functionalized polynorbornenes as an effective alternative to conventional protein/polymer modification strategies and further expand the toolbox for protein bioconjugates.

Design of virus-based nanomaterials for medicine, biotechnology, and energy

“…106 (ROMP) is another method for biocompatible polymer synthesis, and it was utilized to prepare water-soluble polynorbornene-based polymers with strict size and architecture control, which had a good safety profile when attached to Qβ and delivered to fibroblast cells. 107 …”

Highly efficient reversible addition-fragmentation chain-transfer polymerization in ethanol/water via flow chemistry

“…It is well known that the high thermal exchange efficiency of a flow reactor not only provides products with homogeneous properties, but also leads to a high‐efficiency polymerization process . Herein, PEGMEMA 300 was selected as the monomer for RAFT polymerization in aqueous system due to its unique properties and hence broad application range from biomaterials to energy storage devices . Due to the low solubility of RAFT‐CTA in pure water, an aqueous solution with 50% ethanol was prepared for the polymerization.…”

“…With well‐controlled RAFT polymerization process, high‐efficiency polymerization manner and continuous reaction nature, the RAFT polymerization in a pressure‐tunable flow reactor may provide a scalable and efficient method to produce homopolymers and block polymers with well‐defined properties in a highly efficient way. Moreover, due to the wide application of polymeric materials based on PEGMEMA, we anticipate that the successful demonstration of high‐efficiency synthesis at elevated temperature will also be beneficial to polymer synthesis for biomaterials and energy storage devices in a high‐efficiency manner.…”

Photochemistry for Well‐Defined Polymers in Aqueous Media: From Fundamentals to Polymer Nanoparticles to Bioconjugates

“…In addition, the development of efficient metal‐free and other photocatalytic RAFT systems will likely lead to efficient aqueous polymerization under biologically applicable conditions. These research topics are anticipated to be a focus area in the future as the bioconjugate field moves toward industrially relevant enzymatic proteins and bioconjugates with biomedical applications …”