In the last few years, solid-state NMR has matured into a method to investigate the structure of non-soluble proteins such as amyloid aggregates. This opens the possibility to study amyloid–small molecule interactions, and allows better to understand the structural basis of the promiscuous binding of dyes such as Thioflavin T and Congo red. Numerous small molecules have been suggested as potential inhibitors of amyloid aggregation, as they interfere with amyloid protein solubility and its aggregation behavior. The structural basis of the interaction is in most cases, however, only poorly understood. Structural information can potentially assist in the rational design of inhibitors targeting amyloidogenic peptides and proteins to counteract amyloid associated neurotoxicity. This chapter aims to summarize the progress that has been made in NMR investigations involving amyloid–ligand interactions.
