Solid-phase synthesis of protein-polymers on reversible immobilization supports

Hironobu Murata, Sheiliza Carmali, Stefanie L Baker, Krzysztof Matyjaszewski, Alan J Russell

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
4 Downloads (Pure)


Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred when chemistry was developed to grow nucleic acids and peptides from reversibly immobilized precursors. Protein-polymer conjugates, however, have always been synthesized in solution in multi-step, multi-day processes that couple innovative chemistry with challenging purification. Here we report the generation of protein-polymer hybrids synthesized by protein-ATRP on reversible immobilization supports (PARIS). We utilized modified agarose beads to covalently and reversibly couple to proteins in amino-specific reactions. We then modified reversibly immobilized proteins with protein-reactive ATRP initiators and, after ATRP, we released and analyzed the protein polymers. The activity and stability of PARIS-synthesized and solution-synthesized conjugates demonstrated that PARIS was an effective, rapid, and simple method to generate protein-polymer conjugates. Automation of PARIS significantly reduced synthesis/purification timelines, thereby opening a path to changing how to generate protein-polymer conjugates.

Original languageEnglish
Article number845
JournalNature Communications
Issue number1
Publication statusPublished - 27 Feb 2018
Externally publishedYes


  • Peptides/chemical synthesis
  • Polymerization
  • Polymers/chemical synthesis
  • Proteins/chemical synthesis
  • Solid-Phase Synthesis Techniques


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