Chiral Metallohelical Complexes Enantioselectively Target Amyloid β for Treating Alzheimer's Disease

Abstract

Stereochemistry is a very important issue for the pharmaceutical industry and can determine drug efficacy. The design and synthesis of small molecules, especially chiral molecules, which selectively target and inhibit amyloid-beta (A beta) aggregation, represent valid therapeutic strategies for treatment of Alzheimer's disease (AD). Herein we report that two triple-helical dinuclear metallosupramolecular complexes can act as a novel class of chiral amyloid-beta inhibitors. Through targeting alpha/beta-discordant stretches at the early steps of aggregation, these metal complexes can enantioselectively inhibit A beta aggregation, which is demonstrated using fluorescent living cell-based screening and multiple biophysical and biochemical approaches. To the best of our knowledge, this is the first report of enantioselective inhibition of A beta aggregation. Intriguingly, as a promising candidate for A