Aβ1-42 C-terminus fragment derived peptides prevent the self-assembly of the parent peptide

In an attempt to design Ab aggregation inhibitors to combat Alzheimer's disease, herein we report a full peptide scan performed on a pentapeptide fragment (A beta(38-42)) derived from the C-terminus of A beta(1-42) peptide. More than thirty new peptides were synthesized and tested for their inhibition activity towards Ab self-assembly. In the cell viability assay, when co-incubated with Ab, three peptides were found to completely prevent the toxicity induced by Ab aggregation. Most active pentapeptides were also studied by ThT fluorescence assay and the results were well correlated to the MTT study. The inhibition potential of a pentapeptide (15) was further confirmed by CD spectroscopy and transmission electron microscopy.