Xu, L;
Raabe, M;
Zegota, MM;
Nogueira, JCF;
Chudasama, V;
Kuan, SL;
Weil, T;
(2020)
Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation.
Organic & Biomolecular Chemistry
10.1039/c9ob02687h.
(In press).
Preview |
Text
c9ob02687h.pdf - Published Version Download (1MB) | Preview |
Abstract
An inverse electron demand Diels–Alder reaction between tetrazine and trans-cyclooctene (TCO) holds great promise for protein modification and manipulation. Herein, we report the design and synthesis of a tetrazine-based disulfide rebridging reagent, which allows the site-selective installation of a tetrazine group into disulfide-containing peptides and proteins such as the hormone somatostatin (SST) and the antigen binding fragment (Fab) of human immunoglobulin G (IgG). The fast and efficient conjugation of the tetrazine modified proteins with three different TCO-containing substrates to form a set of bioconjugates in a site-selective manner was successfully demonstrated for the first time. Homogeneous, well-defined bioconjugates were obtained underlining the great potential of our method for fast bioconjugation in emerging protein therapeutics. The formed bioconjugates were stable against glutathione and in serum, and they maintained their secondary structure. With this work, we broaden the scope of tetrazine chemistry for site-selective protein modification to prepare well-defined SST and Fab conjugates with preserved structures and good stability under biologically relevant conditions.
Type: | Article |
---|---|
Title: | Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1039/c9ob02687h |
Publisher version: | https://doi.org/10.1039/c9ob02687h |
Language: | English |
Additional information: | This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. http://creativecommons.org/licenses/by/3.0/ |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
URI: | https://discovery.ucl.ac.uk/id/eprint/10090650 |
Archive Staff Only
View Item |