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Human insulin fibrillogenesis in the presence of epigallocatechin gallate and melatonin: Structural insights from a biophysical approach
- Carbonaro, M., Ripanti, F., Filabozzi, A., Minicozzi, V., Stellato, F., Placidi, E., Morante, S., Di Venere, A., Nicolai, E., Postorino, P., Nucara, A.
- International journal of biological macromolecules 2018 v.115 pp. 1157-1164
- Raman spectroscopy, atomic force microscopy, epigallocatechin gallate, fluorescence, humans, hydrophobicity, infrared spectroscopy, insulin, light scattering, melatonin
- 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.