Novel aggregation-specific fluorogen monitors prefibrillar protein aggregation by fluorescence polarisation (FP)

Manjeet Kumar (1), Yuning Hong (2,3), David C. Thorn (1), Heath Ecroyd (4), John A. Carver (1) (1) Research School of Chemistry, The Australian National University, Australia, (2) Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Australia, (3) School of Chemistry, The University of Melbourne, Australia, (4) School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia 07/2018

Highly ordered protein aggregates, termed amyloid fibrils, are associated with a broad range of diseases, many of which are neurodegenerative, for example, Alzheimer’s and Parkinson’s. The transition from soluble, functional protein to insoluble amyloid fibril occurs via a complex process involving the initial generation of highly dynamic early stage aggregates or prefibrillar species. Prefibrillar species (dimers, tetramers etc.) are proposed to play a key role in the cytotoxicity of amyloid fibrils. Therefore, novel probes that have broad applicability in the detection of prefibrillar species of amyloidogenic proteins are actively being sought.

Recently, a novel broad-spectrum fluorescent probe was presented: (bis(triphenylphosphonium) tetraphenylethene (TPE-TPP)), with emission characteristics that are eminently suited to monitoring prefibrillar aggregation of various protein species using various fluorescence techniques. It is shown that TPE-TPP-based FP measurements can monitor the fibrillar assembly of a variety of amyloid fibril-forming proteins in situ.


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