Polymeric “Clickase” Accelerates the Copper Click Reaction of Small Molecules, Proteins, and Cells

• Published in: Journal of the American Chemical Society Vol. 141; no. 24; pp. 9693 - 9700
• Main Authors: Chen, Junfeng, Wang, Jiang, Li, Ke, Wang, Yuhan, Gruebele, Martin, Ferguson, Andrew L, Zimmerman, Steven C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.06.2019
• Subjects: active sites; alkynes; azides; catalysts; catalytic activity; copper; cycloaddition reactions; hydrophobicity; nanoparticles; polymers; polysaccharides; proteins; water solubility
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.9b04181

Recent work has shown that polymeric catalysts can mimic some of the remarkable features of metalloenzymes by binding substrates in proximity to a bound metal center. We report here an unexpected role for the polymer: multivalent, reversible, and adaptive binding to protein surfaces allowing for accelerated catalytic modification of proteins. The catalysts studied are a group of copper-containing single-chain polymeric nanoparticles (CuI–SCNP) that exhibit enzyme-like catalysis of the copper-mediated azide–alkyne cycloaddition reaction. The CuI–SCNP use a previously observed “uptake mode”, binding small-molecule alkynes and azides inside a water-soluble amphiphilic polymer and proximal to copper catalytic sites, but with unprecedented rates. Remarkably, a combined experimental and computational study shows that the same CuI–SCNP perform a more efficient click reaction on modified protein surfaces and cell surface glycans than do small-molecule catalysts. The catalysis occurs through an “attach mode” where the SCNPs reversibly bind protein surfaces through multiple hydrophobic and electrostatic contacts. The results more broadly point to a wider capability for polymeric catalysts as artificial metalloenzymes, especially as it relates to bioapplications.