Tunable inhibition of β-amyloid peptides by fast green molecules* *Project supported by the National Natural Science Foundation of China (Grand No. 11804174), Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Sciences, and K. C. Wong Magna Fund in Ningbo University.

Abstract

The aggregation of β-amyloid (Aβ) protein into toxic intermediates and mature fibrils is considered to be one of the main causes of Alzheimer’s disease (AD). Small molecules as one of blockers are expected to be the potential drug treatment for the disease. However, the nucleation process in molecular assembly is less informative in the literatures. In this work, the formation of Aβ(16-22) peptides was investigated with the presence of small molecule of fast green (FG) at the initial aggregation stage. The results exhibited the tunable inhibitory ability of FG molecules on Aβ(16-22) peptides. Atomic force microscopy (AFM) demonstrated that the inhibitory effect would be dependent on the dose of FG molecules, which could delay the lag time (nucleation) and form single layer conjugates. Spectral measurements further showed that the β-sheet secondary structure of Aβ(16-22) reduced dramatically after the presence of FG molecules. Instead, non-β-sheet nanosheets were formed when the FG/Aβ(16-22) ratio reached 1:1. In addition, the cytotoxicity of aggregates reduced greatly with the presence of FG molecules compared with the Aβ(16-22) fibrils. Overall, this study provided a method for suppressing the toxic amyloid aggregates by FG molecules efficiently, and also showed a strategy for fabrication of two-dimensional materials by small molecules.