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Locked by Design: A Conformationally Constrained Transglutaminase Tag Enables Efficient Site‐Specific Conjugation
Author(s) -
Siegmund Vanessa,
Schmelz Stefan,
Dickgiesser Stephan,
Beck Jan,
Ebenig Aileen,
Fittler Heiko,
Frauendorf Holm,
Piater Birgit,
Betz Ulrich A. K.,
Avrutina Olga,
Scrima Andrea,
Fuchsbauer HansLothar,
Kolmar Harald
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201504851
Subject(s) - tissue transglutaminase , chemistry , intramolecular force , disulfide bond , binding site , active site , enzyme , stereochemistry , substrate (aquarium) , monoclonal antibody , substrate specificity , biochemistry , antibody , biology , ecology , immunology
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.