Common benzothiazole and benzoxazole fluorescent DNA intercalators for studying Alzheimer Aβ1-42 and prion amyloid peptides.

Abstract

Amyloids are fibrillar protein aggregates associated with a number of neurodegenerative pathologies including Alzheimer and Creutzfeldt-Jakob disease. The study of amyloids is usually based on fluorescence with the dye thioflavin-T. Although a number of amyloid binding compounds have been synthesized, many are nonfluorescent or not readily available for research use. Here we report on a class of commercial benzothiazole/benzoxazole containing fluorescent DNA intercalators from Invitrogen that possess the ability to bind amyloid Aβ1-42 peptide and hamster prion. These dyes fluoresce from 500-750 nm and are available as dimers or monomers. We demonstrate that these dyes can be used as acceptors for thioflavin-T fluorescence resonance energy transfer as well as reporter groups for binding studies with Congo red and chrysamine G. As more potential therapeutic compounds for these diseases are generated, there is a need for simple and inexpensive methods to monitor their interactions with amyloids. The fluorescent dyes reported here are readily available and can be used as tools for biochemical studies of amyloid structures and in vitro screening of potential therapeutics.