Combining Solid-State NMR with Structural and Biophysical Techniques to Design Challenging Protein-Drug Conjugates.

Autor: Cerofolini L; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Vasa K; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Bianconi E; Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti n.48, 06123, Perugia, Italy., Salobehaj M; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Cappelli G; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Bonciani A; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Licciardi G; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Pérez-Ràfols A; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Giotto Biotech s.r.l, Sesto Fiorentino, Via della Madonna del Piano 6, 50019, Florence, Italy., Padilla-Cortés L; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Antonacci S; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Rizzo D; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Ravera E; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Viglianisi C; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Calderone V; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Parigi G; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Luchinat C; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.; Giotto Biotech s.r.l, Sesto Fiorentino, Via della Madonna del Piano 6, 50019, Florence, Italy., Macchiarulo A; Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti n.48, 06123, Perugia, Italy., Menichetti S; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy., Fragai M; Magnetic Resonance Centre (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Aug 01; Vol. 62 (31), pp. e202303202. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1002/anie.202303202
Abstrakt: Several protein-drug conjugates are currently being used in cancer therapy. These conjugates rely on cytotoxic organic compounds that are covalently attached to the carrier proteins or that interact with them via non-covalent interactions. Human transthyretin (TTR), a physiological protein, has already been identified as a possible carrier protein for the delivery of cytotoxic drugs. Here we show the structure-guided development of a new stable cytotoxic molecule based on a known strong binder of TTR and a well-established anticancer drug. This example is used to demonstrate the importance of the integration of multiple biophysical and structural techniques, encompassing microscale thermophoresis, X-ray crystallography and NMR. In particular, we show that solid-state NMR has the ability to reveal effects caused by ligand binding which are more easily relatable to structural and dynamical alterations that impact the stability of macromolecular complexes.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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