RESUMO
The formation of Aß into amyloid fibrils was closely connected to AD, therefore, the Aß aggregates were the primary therapeutic targets against AD. Previous studies demonstrated that epicatechin-3-gallate (ECG), which possessed a gallate moiety, exhibited a greater ability to disrupt the preformed Aß amyloid fibrils than epicatechin (EC), indicating that the gallate moiety was crucial. In the present study, the molecular mechanisms were investigated. Our results demonstrated that ECG had more potent disruptive impacts on the ß-sheet structure and K28-A42 salt bridges than EC. We found that ECG significantly interfered the interactions between Peptide-4 and Peptide-5. However, EC could not. The disruption of K28-A42 salt bridges by ECG was mainly due to the interactions between ECG and the hydrophobic residues located at C-terminus. Interestingly, EC disrupted the K28-A42 salt bridges by the interactions with C-terminal hydrophobic residues and the cation-π interactions with K28. Moreover, our results indicated that hydrophobic interactions, H-bonds, π-π interactions and cation-π interactions between ECG and the bend of L-shaped region caused the disaggregation of interactions between Peptide-4 and Peptide-5. Significantly, gallate moiety in ECG had contributed tremendously to the disaggregation. We believed that our findings could be useful for designing prospective drug candidates targeting AD.
