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

作者：Reinke Ashley A; Seh Han Yiau; Gestwicki Jason E^*

来源：Bioorganic & Medicinal Chemistry Letters, 2009, 19(17): 4952-4957.

DOI：10.1016/j.bmcl.2009.07.082

• Alzheimer's disease
• Neurodegeneration
• Protein misfolding
• Thioflavin T
• Fluorescence

Aggregated amyloid-beta (A beta) 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 A beta ligands against pre-formed oligomers and fibrils. In these studies, we found that the fluorescence of five indole-based compounds was selectively quenched (similar to 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.

• 出版日期2009-9-1