Details

Autor(en) / Beteiligte

• Carbonaro, M.
• Ripanti, F.
• Filabozzi, A.
• Minicozzi, V.
• Stellato, F.
• Placidi, E.
• Morante, S.
• Di Venere, A.
• Nicolai, E.
• Postorino, P.
• Nucara, A.

Titel

Human insulin fibrillogenesis in the presence of epigallocatechin gallate and melatonin: Structural insights from a biophysical approach

Ist Teil von

• International journal of biological macromolecules, 2018-08, Vol.115, p.1157-1164

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Fibrillogenesis of monomeric human insulin in the presence or absence of (-)-epigallocatechin-3-gallate and melatonin was here investigated using a multi-technique approach. Results from Raman and Infrared spectroscopy pointed out that a high content of intermolecular β-sheet aggregates is formed after long-term incubation. However, near UV experiments, Dynamic Light Scattering, Thioflavin-T fluorescence measurements and Atomic Force Microscopy revealed that the kinetics from native-to-fibrillar state of insulin is hampered only in the presence of (-)-epigallocatechin-3-gallate. Molecular dynamic simulations indicated that this compound binds near the B11–B18 protein segment, where hydrophobic residues responsible for the beginning of cooperative aggregation are located. Such a preferential binding region is not recognized by melatonin, a highly mobile molecule, which indeed does not affect fibril formation. The results of the present study demonstrate that (-)-epigallocatechin-3-gallate interferes with the insulin nucleation phase, giving rise to amorphous aggregates in the early stages of the aggregation process.