Centres Científics i Tecnològics UB

Noticias

16.04.2020

Publicación del artículo "Calorimetric Studies of Binary and Ternary Molecular Interactions between Transthyretin, Aβ Peptides, and Small-Molecule Chaperones toward an Alternative Strategy for Alzheimer’s Disease Drug Discovery."

El Dr. Rafel Prohens, responsable de la Tecnología de Polimorfismo y Calorimetría de los CCiTUB, ha publicado el artículo "Calorimetric Studies of Binary and Ternary Molecular Interactions between Transthyretin, Aβ Peptides, and Small-Molecule Chaperones toward an Alternative Strategy for Alzheimer’s Disease Drug Discovery” en la revista Journal of Medicinal Chemistry.

El resumen del artículo es el siguiente:

"Transthyretin (TTR) modulates the deposition, processing, and toxicity of Abeta (Aβ) peptides. We have shown that this effect is enhanced in mice by treatment with small molecules such as iododiflunisal (IDIF, 4), a good TTR stabilizer. Here, we describe the thermodynamics of the formation of binary and ternary complexes among TTR, Aβ(1–42) peptide, and TTR stabilizers using isothermal titration calorimetry (ITC). A TTR/Aβ(1–42) (1:1) complex with a dissociation constant of Kd = 0.94 μM is formed; with IDIF (4), this constant improves up to Kd = 0.32 μM, indicating the presence of a ternary complex TTR/IDIF/Aβ(1–42). However, with the drugs diflunisal (1) or Tafamidis (2), an analogous chaperoning effect could not be observed. Similar phenomena could be recorded with the shorter peptide Aβ(12–28) (7). We propose the design of a simple assay system for the search of other chaperones that behave like IDIF and may become potential candidate drugs for Alzheimer’s disease (AD)."

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