Charged Tubular Supramolecule Boosting Multivalent Interactions for the Drastic Suppression of Aβ Fibrillation

Anti-A beta therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD). However, suppressing A beta aggregation and disintegrating mature fibrils simultaneously remains a great challenge. In this work, we developed a new strategy using a charged tubular supramolecule (CTS) with pillar[5]arene as the backbone and modifying amino and carboxyl groups at the tubular terminals (noted as CTS-A, CTS-A/C, and CTS-C, respectively) to suppress A beta fibrillation for the first time. According to the spectroscopic and microscopic characterizations, A beta(40) fibrillation can be efficiently suppressed by CTS-A in a very low inhibitor:peptide (I:P) molar ratio (1:10). A greatly alleviated cytotoxic effect of A beta peptides after the inhibition or disaggregation process is further disclosed. The well-organized supramolecular structure drives multivalent interaction and gains enhanced efficiency on amyloid fibrillar modulation. These results open a new path for the design of supramolecules in the application of AD treatment.