Rational Design of a Cocktail of Inhibitors against Aβ Aggregation

It has been reported that many molecules could inhibit the aggregation of A beta (amyloid-beta) through suppressing either primary nucleation, secondary nucleation, or elongation processes. In order to suppress multiple pathways of A beta aggregation, we screened 23 small molecules and found two types of inhibitors with different inhibiting mechanisms based on chemical kinetics analysis. Trp-glucose conjugates (AS2) could bind with fibril ends while natural products (D3 and D4) could associate with monomers. A cocktail of these two kinds of molecules achieved co-inhibition of various fibrillar species and avoid unwanted interference.