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11 results on '"Hartmann, David"'

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

Author

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

Published
2019
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9. Totalsynthese von Myrtucommulon A

Author

Müller, Hans, primary, Paul, Michael, additional, Hartmann, David, additional, Huch, Volker, additional, Blaesius, Dagmar, additional, Koeberle, Andreas, additional, Werz, Oliver, additional, and Jauch, Johann, additional

Published
2010
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10. Total Synthesis of Myrtucommulone A

Author

Müller, Hans, primary, Paul, Michael, additional, Hartmann, David, additional, Huch, Volker, additional, Blaesius, Dagmar, additional, Koeberle, Andreas, additional, Werz, Oliver, additional, and Jauch, Johann, additional

Published
2010
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11. Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine-Selective Protein Modification and Charge Modulation

Author

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 PJ, Jiménez-Osés, Gonzalo, and Bernardes, Gonçalo JL

Subjects
microfluidics, antibody-drug conjugates, bioconjugation, cysteine, 3. Good health, protein modification
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.

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