A Ligand-Based NMR Screening Approach for the Identification and Characterization of Inhibitors and Promoters of...

Over the years a significant amount of effort has been put into the development of rapid and reliable methods to monitor the aggregation dynamics of the β_1-42 amyloid peptide in real time. We present an alternative approach based on a suitable reporter or spy molecule and three different NMR experiments: WaterLOGSY, ¹ H selective T₁ filter, and ¹⁹ F T₂ filter, for monitoring the initial self-aggregation process kinetics of the β_1-42 amyloid peptide and identifying molecules that retard or accelerate the self-aggregation process. Although the proposed method is not a high-throughput assay, it avoids problems associated with interference events that are sometimes observed in fluorescence-based assays.