Efficient Site-Specific Antibody-Drug Conjugation by Engineering a Nature-Derived Recognition Tag for Microbial Transglutaminase.


Journal

Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360

Informations de publication

Date de publication:
16 09 2019
Historique:
received: 18 02 2019
revised: 28 04 2019
pubmed: 3 5 2019
medline: 22 9 2020
entrez: 3 5 2019
Statut: ppublish

Résumé

Microbial transglutaminase (mTG) has recently emerged as a powerful tool for antibody engineering. In nature, it catalyzes the formation of amide bonds between glutamine side chains and primary amines. Being applied to numerous research fields from material sciences to medicine, mTG enables efficient site-specific conjugation of molecular architectures that possess suitable recognition motifs. In monoclonal antibodies, the lack of native transamidation sites is bypassed by incorporating specific peptide recognition sequences. Herein, we report a rapid and efficient mTG-catalyzed bioconjugation that relies on a novel recognition motif derived from its native substrate Streptomyces papain inhibitor (SPI

Identifiants

pubmed: 31044494
doi: 10.1002/cbic.201900101
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
Bacterial Proteins 0
Immunoconjugates 0
Oligopeptides 0
Transglutaminases EC 2.3.2.13
Trastuzumab P188ANX8CK
monomethyl auristatin E V7I58RC5EJ

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2411-2419

Subventions

Organisme : Bundesministerium für Bildung und Forschung
ID : NANOKAT II
Pays : International

Informations de copyright

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Aileen Ebenig (A)

Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.

Norbert Egon Juettner (NE)

Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, Stephanstrasse 7, 64295, Darmstadt, Germany.
Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 10, 64287, Darmstadt, Germany.

Lukas Deweid (L)

Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.

Olga Avrutina (O)

Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.

Hans-Lothar Fuchsbauer (HL)

Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, Stephanstrasse 7, 64295, Darmstadt, Germany.

Harald Kolmar (H)

Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.

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