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1.
Angew Chem Int Ed Engl ; 62(31): e202303202, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37276329

RESUMEN

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.


Asunto(s)
Proteínas Portadoras , Imagen por Resonancia Magnética , Humanos , Preparaciones Farmacéuticas , Espectroscopía de Resonancia Magnética , Proteínas Portadoras/química , Cristalografía por Rayos X
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