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

Abstract: 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.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine‐Selective Protein Modification and Charge Modulation ; volume:58 ; number:20 ; year:2019 ; pages:6640-6644 ; extent:5 ; Angewandte Chemie / International edition. International edition ; 58, Heft 20 (2019), 6640-6644 (gesamt 5)

Beteiligte, Orts- und Zeitangaben

• Urheber: Matos, Maria J. ; Navo, Claudio D. ; Hakala, Tuuli ; Ferhati, Xhenti ; Guerreiro, Ana ; Hartmann, David ; Bernardim, Barbara ; Saar, Kadi L. ; Compañón, Ismael ; Corzana, Francisco ; Knowles, Tuomas P. J. ; Jiménez‐Osés, Gonzalo ; Bernardes, Gonçalo J. L.

Weitere Informationen

• DOI: 10.1002/anie.201901405
• URN: urn:nbn:de:101:1-2022071211102207588259
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:23 MESZ