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Chembiochem. 2017 Oct 5;18(19):1923-1927. doi: 10.1002/cbic.201700188. Epub 2017 Aug 29.

Dual, Site-Specific Modification of Antibodies by Using Solid-Phase Immobilized Microbial Transglutaminase.

Author information

1
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
2
Laboratory of Polymer Chemistry, Department of Materials, ETH Zürich, Vladimir-Prelog-Weg 5, 8093, Zürich, Switzerland.
3
Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
4
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.

Abstract

Microbial transglutaminase (MTG) was stably solid-phase immobilized on glass microbeads by using a second-generation dendronized polymer. Immobilized MTG enabled the efficient generation of site-specifically conjugated proteins, including antibody fragments, as well as whole antibodies through distinct glutamines and, unprecedentedly, also through lysines with various bifunctional substrates with defined stoichiometries. With this method, we generated dual, site-specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling-a strategy anticipated to design antibodies for imaging and simultaneous therapy. Furthermore, we provide evidence that immobilized MTG features higher siteselectivity than soluble MTG.

KEYWORDS:

antibodies; bioconjugation; immobilization; site-specific modification; transglutaminase

PMID:
28771896
DOI:
10.1002/cbic.201700188
[Indexed for MEDLINE]

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