Hetero-Diels-Alder Cycloaddition with RAFT Polymers as Bioconjugation Platform

Ana Beloqui; Shivshankar R Mane; Marcel Langer; Mathias Glassner; Dennis M Bauer; Ljiljana Fruk; Christopher Barner-Kowollik; Guillaume Delaittre

doi:10.1002/anie.202005747

Hetero-Diels-Alder Cycloaddition with RAFT Polymers as Bioconjugation Platform

Angew Chem Int Ed Engl. 2020 Nov 2;59(45):19951-19955. doi: 10.1002/anie.202005747. Epub 2020 Sep 2.

Authors

Ana Beloqui^{1

2

3

4}, Shivshankar R Mane^{1

2}, Marcel Langer², Mathias Glassner², Dennis M Bauer⁵, Ljiljana Fruk^{5

6}, Christopher Barner-Kowollik^{2

7

8}, Guillaume Delaittre^{1

2

9}

Affiliations

¹ Institute of Biological and Chemical Systems (IBCS), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
² Macromolecular Architectures, Institute for Chemical Technology and Polymer Chemistry (ITCP), Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76131, Karlsruhe, Germany.
³ Department of Applied Chemistry (UPV/EHU), Avda. Manuel de Lardizabal 3, E-20018, Donostia - San Sebastian, Spain.
⁴ IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, E-48013, Bilbao, Spain.
⁵ Center for Functional Nanostructures (CFN), Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Straße 1a, 76131, Karlsruhe, Germany.
⁶ Department of Chemical Engineering and Biotechnology, University of Cambridge, West Cambridge Site, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
⁷ Centre for Materials Science, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD, 4000, Australia.
⁸ School of Chemistry and Physics, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD, 4000, Australia.
⁹ Organic Functional Molecules, Organic Chemistry, University of Wuppertal, Gaußstrasse 20, 42119, Wuppertal, Germany.

Abstract

We introduce the bioconjugation of polymers synthesized by RAFT polymerization, bearing no specific functional end group, by means of hetero-Diels-Alder cycloaddition through their inherent terminal thiocarbonylthio moiety with a diene-modified model protein. Quantitative conjugation occurs over the course of a few hours, at ambient temperature and neutral pH, and in the absence of any catalyst. Our technology platform affords thermoresponsive bioconjugates, whose aggregation is solely controlled by the polymer chains.

Keywords: Diels-Alder cycloaddition; bioconjugation; end group; polymer; protein.

MeSH terms

Catalysis
Cycloaddition Reaction*
Hydrogen-Ion Concentration
Polymers / chemistry*
Temperature

Substances

Polymers