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

Nat Commun. 2018 Feb 27;9(1):845. doi: 10.1038/s41467-018-03153-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Peptides
  • Polymers
  • Proteins