Département de chimie moléculaire

Amyloid $\beta$ peptide (A$\beta$) fibril formation is widely believed to be the causative event of Alzheimer's disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the prodn. and aggregation of A$\beta$. Herein the authors present a high-throughput screening tool to generate novel hit compds. that block A$\beta$ fibril formation. This tool is an application for the fibril model (A$\beta$16-37Y20K22K24)4, which is a covalent assembly of four A$\beta$ fragments. With this tool, screening studies are complete within one hour, as opposed to days with native A$\beta$1-40 A Z' factor of 0.84±0.03 was detd. for fibril formation and inhibition, followed by the reporter mol. thioflavin T. Herein the authors also describe the anal. of a broad range of reported inhibitors and noninhibitors of A$\beta$ fibril formation to test the validity of the system. [on SciFinder(R)]