Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine¿Selective Protein Modification and Charge Modulation

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Matos, MJ (Author) Other; Navo, CD (Author) Other; Hakala, T (Author) Other; Ferhati, X (Author) Other; Guerreiro, A (Author) Other; Hartmann, D (Author) Other; Bernardim, B (Author) Other; Saar, KL (Author) Other; Compañón, I (Author) Other; Corzana, F (Author) Other; Knowles, TPJ (Author) Other; Jiménez¿Osés, G (Author) Other; Bernardes, GJL (Author) Other

Journal

Title: Angewandte Chemie - International Edition

Vol. 58

Pages: 6640-6644

ISSN: 1433-7851

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-00V-3S1

DOI: 10.1002/anie.201901405

Abstract (EN): Quaternized vinyl- and alkynyl-pyridine reagents were shown to react in an ultrafast and selective manner with several cysteine-tagged proteins at near-stoichiometric quantities. We have demonstrated that this method can effectively create a homogenous antibody-drug conjugate that features a precise drug-to-antibody ratio of 2, which was stable in human plasma and retained its specificity towards Her2+ cells. Finally, the developed warhead introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl- and alkynyl-pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition and as tools to profile cysteine reactivity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5