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A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well-Defined Protein-Protein Conjugates

preprint
submitted on 22.11.2019 and posted on 26.11.2019 by Mathis Baalmann, Laura Neises, Sebastian Bitsch, Hendrik Schneider, Lukas Deweid, Nadja Ilkenhans, Martin Wolfring, Michael J. Ziegler, Philipp Werther, Jonas Wilhelm, Harald Kolmar, Richard Wombacher
A highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels-Alder cycloaddition with inverse electron demand (DAinv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines.

Funding

DFG SPP1623

History

Email Address of Submitting Author

wombacher@uni-heidelberg.de

Institution

Ruprecht-Karls University Heidelberg

Country

Germany

ORCID For Submitting Author

0000-0002-3027-7778

Declaration of Conflict of Interest

non

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