Abnormal deposition of protein aggregates with "amyloid" β-sheet enriched fibrillar structure is a pathological hallmark of a plethora of important diseases, among them Alzheimer's, Parkinson's and Huntington's diseases, type II diabetes, and the prion-transmitted spongiform encephalopathies. Understanding these diseases' pathology and progress, as well as developing treatments, requires us to find new ways of tracking destructive protein assemblies. We propose that oligo(p-phenyleneethynylene) electrolytes (OPEs) represent a new class of promising, protein-conformation-sensitive optical probes with multiple sensing modalities. Here we report a thorough characterization of four OPEs with varying chain lengths and charged groups as fluorescent stains for amyloid fibrils formed in vitro from hen egg white lysozyme. The OPEs tested perform as well as Thioflavin T, the current gold standard dye. Preliminary data indicates that OPEs are also capable of distinguishing between amyloid aggregates formed from different protein monomers. The OPE backbone also has potential as a scaffold for rational design of superior fluorescent ligands for amyloid; we present design principles that can be used to synthesize OPEs with highly desirable properties for three-dimensional in vivo tracking of amyloid aggregates.

Tracking amyloids with fluorescent oligo(p-phenyleneethynylene) electrolytes

249th National Meeting (2015)

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