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ID: ALA1156243

Journal: Bioorg Med Chem Lett

Title: A chemical screening approach reveals that indole fluorescence is quenched by pre-fibrillar but not fibrillar amyloid-beta.

Authors: Reinke AA, Seh HY, Gestwicki JE.

Abstract: Aggregated amyloid-beta (Abeta) peptide is implicated in the pathology of Alzheimer's disease. In vitro and in vivo, these aggregates are found in a variety of morphologies, including globular oligomers and linear fibrils, which possess distinct biological activities. However, known chemical probes, including the dyes thioflavin T and Congo Red, appear to lack selectivity for specific amyloid structures. To identify molecules that might differentiate between these architectures, we employed a fluorescence-based interaction assay to screen a collection of 68 known Abeta ligands against pre-formed oligomers and fibrils. In these studies, we found that the fluorescence of five indole-based compounds was selectively quenched ( approximately 15%) in the presence of oligomers, but remained unchanged after addition of fibrils. These results suggest that indoles might be complementary to existing chemical probes for studying amyloid formation in vitro.

CiteXplore: 19640715

DOI: 10.1016/j.bmcl.2009.07.082