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Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry.

Publication ,  Journal Article
Navarro, LA; French, DL; Zauscher, S
Published in: Bioconjugate chemistry
August 2018

Proteoglycans are important brush-like biomacromolecules, which serve a variety of functions in the human body. While protein-bottlebrush hybrids are promising proteoglycan mimics, many challenges still exist to robustly produce such polymers. In this paper, we report the modular synthesis of protein-brush hybrids containing elastin-like polypeptides (ELP) as model proteins by copper-catalyzed azide-alkyne cycloaddition. We exploit the recently discovered imidazole-1-sulfonyl azide (ISA) in a diazotransfer reaction to introduce an N-terminal azide onto an ELP. Next, we use a click reaction to couple the azido-ELP to an alkyne-terminated amine-rich polymer followed by a second diazotransfer step to produce an azide-rich backbone that serves as a scaffold. Finally, we used a second click reaction to graft alkyne-terminated poly(oligoethylene glycol methacrylate) (POEGMA) bristles to the azide-rich backbone to produce the final protein-bottlebrush hybrid. We demonstrate the effectiveness of this synthetic path at each step through careful characterization with 1H NMR, FTIR, GPC, and diagnostic test reactions on SDS-PAGE. Final reaction products could be consistently obtained for a variety of different molecular weight backbones with final total grafting efficiencies around 70%. The high-yielding reactions employed in this highly modular approach allow for the synthesis of protein-bottlebrush hybrids with different proteins and brush polymers. Additionally, the mild reaction conditions used have the potential to avoid damage to proteins during synthesis.

Duke Scholars

Published In

Bioconjugate chemistry

DOI

EISSN

1520-4812

ISSN

1043-1802

Publication Date

August 2018

Volume

29

Issue

8

Start / End Page

2594 / 2605

Related Subject Headings

  • Spectroscopy, Fourier Transform Infrared
  • Proton Magnetic Resonance Spectroscopy
  • Proteins
  • Polymers
  • Organic Chemistry
  • Humans
  • Electrophoresis, Polyacrylamide Gel
  • Cycloaddition Reaction
  • Copper
  • Click Chemistry
 

Citation

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Navarro, L. A., French, D. L., & Zauscher, S. (2018). Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry. Bioconjugate Chemistry, 29(8), 2594–2605. https://doi.org/10.1021/acs.bioconjchem.8b00309
Navarro, Luis A., Daniel L. French, and Stefan Zauscher. “Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry.Bioconjugate Chemistry 29, no. 8 (August 2018): 2594–2605. https://doi.org/10.1021/acs.bioconjchem.8b00309.
Navarro LA, French DL, Zauscher S. Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry. Bioconjugate chemistry. 2018 Aug;29(8):2594–605.
Navarro, Luis A., et al. “Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry.Bioconjugate Chemistry, vol. 29, no. 8, Aug. 2018, pp. 2594–605. Epmc, doi:10.1021/acs.bioconjchem.8b00309.
Navarro LA, French DL, Zauscher S. Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry. Bioconjugate chemistry. 2018 Aug;29(8):2594–2605.
Journal cover image

Published In

Bioconjugate chemistry

DOI

EISSN

1520-4812

ISSN

1043-1802

Publication Date

August 2018

Volume

29

Issue

8

Start / End Page

2594 / 2605

Related Subject Headings

  • Spectroscopy, Fourier Transform Infrared
  • Proton Magnetic Resonance Spectroscopy
  • Proteins
  • Polymers
  • Organic Chemistry
  • Humans
  • Electrophoresis, Polyacrylamide Gel
  • Cycloaddition Reaction
  • Copper
  • Click Chemistry