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Ring Opening Metathesis Polymerization From the Surface of Proteins

详细技术说明

Ring Opening Metathesis Polymerization (ROMP) is a new chemistry that improves upon PEGylation. In this invention, ROMP was carried out from the surface of a protein under aqueous conditions. App

*Abstract

Ring Opening Metathesis Polymerization (ROMP) is a new chemistry that improves upon PEGylation. In this invention, ROMP was carried out from the surface of a protein under aqueous conditions. Appropriate modification of the protein enables one to create a stable macroinitiator for ROMP to occur. The protein macroinitiator can then be used to polymerize water-soluble norbornenes, oxanorbornenes, or cyclooctenes resulting in high molecular weight protein-polymer conjugates. Full conversion of the macroinitiator is seen and polymerization is complete in minutes. Finally, reactive block copolymers can be synthesized from the protein surface and shown to react post-polymerization using "click" chemistry to efficiently install fluorophores.The ease by which these monomers can be modified offers the potential to incorporate high-performance polymers that could bear imaging agents or small-molecule therapeutics.Additionally, the in vivo properties of polynorbornene-conjugated proteins remain unexplored, and the modification of proteins with these polymers could prove beneficial to pharmacokinetics and biodistribution due to their rigid polyolefin backbones.Applications include drug delivery, molecular imaging, theranostics, and stabilization of therapeutic proteins, both in vitro and in vivo. Next steps in development are expansion of monomer scope, incorporation of therapeutic and/or diagnostic molecules, and site specific modification of protein therapeutics.This work is funded by NSF CHE-1306447, "Bottom-up synthesis of filamentous polymer nanoparticles through bio-templated approaches." It is published as "Protein ROMP: Aqueous Graft-from Ring-Opening Metathesis Polymerization," ACS Macro Letters, 2015, 4, p969-973.A provisional patent application has been filed.

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美国