A Ligand‐Based NMR Screening Approach for the Identification and Characterization of Inhibitors and Promoters of Amyloid Peptide Aggregation

Abstract

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 amyloid peptide in real time. We present an alternative approach based on a suitable reporter or spy molecule and three different NMR experiments: WaterLOGSY, H selective T filter, and F T filter, for monitoring the initial self-aggregation process kinetics of the β 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.

Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects

“…Negative LOGSY effects (positive NOE), as shown in Figure , are indicative of absence of aggregation, whereas positive LOGSY effects (negative NOE) are indicative of aggregation. Recently, this experiment has been used to study aggregation mechanisms as a function of time and to derive the kinetics of the aggregating process …”