Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry.
Journal Article (Journal Article)
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 1 H 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.
Full Text
Duke Authors
Cited Authors
- Navarro, LA; French, DL; Zauscher, S
Published Date
- August 2018
Published In
Volume / Issue
- 29 / 8
Start / End Page
- 2594 - 2605
PubMed ID
- 30001617
Electronic International Standard Serial Number (EISSN)
- 1520-4812
International Standard Serial Number (ISSN)
- 1043-1802
Digital Object Identifier (DOI)
- 10.1021/acs.bioconjchem.8b00309
Language
- eng