Polymeric "clickase" Accelerates the Copper Click Reaction of Small Molecules, Proteins, and Cells

Junfeng Chen, Jiang Wang, Ke Li, Yuhan Wang, Martin Gruebele, Andrew L. Ferguson, Steven C. Zimmerman

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)9693-9700
Number of pages8
JournalJournal of the American Chemical Society
Issue number24
StatePublished - Jun 19 2019

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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