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Locked by Design: A Conformationally Constrained Transglutaminase Tag Enables Efficient Site-Specific Conjugation

Authors :
Olga Avrutina
Stephan Dickgiesser
Holm Frauendorf
Andrea Scrima
Stefan Schmelz
Hans-Lothar Fuchsbauer
Aileen Ebenig
Heiko Fittler
Harald Kolmar
Birgit Piater
Jan Beck
Vanessa Siegmund
Ulrich A. K. Betz
Source :
Angewandte Chemie (International ed. in English). 54(45)
Publication Year :
2015

Abstract

Based on the crystal structure of a natural protein substrate for microbial transglutaminase, an enzyme that catalyzes protein crosslinking, a recognition motif for site-specific conjugation was rationally designed. Conformationally locked by an intramolecular disulfide bond, this structural mimic of a native conjugation site ensured efficient conjugation of a reporter cargo to the therapeutic monoclonal antibody cetuximab without erosion of its binding properties.

Details

ISSN :
15213773
Volume :
54
Issue :
45
Database :
OpenAIRE
Journal :
Angewandte Chemie (International ed. in English)
Accession number :
edsair.doi.dedup.....79d91bb7e93c5fa78c2aedd7cd82f61b