A Fluorescent Pentameric Thiophene Derivative Detects in Vitro-Formed Prefibrillar Protein Aggregates

Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of their likely role in the mechanism of fibril formation and because of the growing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. Herein, we explore the use of an anionic oligothiophene derivative, p-FTAA, for detection of prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins (insulin, lysozyme, and prion protein). p-FTAA generally detected prefibrillar protein aggregates that could not be detected by thioflavine T fluorescence and in addition showed high fluorescence when bound to mature fibrils. Second, the kinetics of protein aggregation or the formation of amyloid fibrils of insulin was not extensively influenced by the presence of various concentrations of p-FTAA. These results establish the use of p-FTAA as an additional tool for studying the process of protein aggregation.

Simon, RozalynLinköpings universitet,Organisk Kemi,Tekniska fakulteten(Swepub:liu)rozsi29 (författare)
Nyström, SofieLinköpings universitet,Biokemi,Tekniska högskolan(Swepub:liu)sofny42 (författare)
Konradsson, PeterLinköpings universitet,Organisk Kemi,Tekniska högskolan(Swepub:liu)petko14 (författare)
Åslund, AndreasLinköpings universitet,Organisk Kemi,Tekniska högskolan(Swepub:liu)andas82 (författare)
Nilsson, PeterLinköpings universitet,Organisk Kemi,Tekniska högskolan(Swepub:liu)petni61 (författare)
Linköpings universitetBiokemi (creator_code:org_t)

Ingår i:BIOCHEMISTRY: ACS American Chemical Society49:32, s. 6838-68450006-29601520-4995

Av författaren/redakt...: Hammarström, Per; Simon, Rozalyn; Nyström, Sofie; Konradsson, Pete ...; Åslund, Andreas; Nilsson, Peter

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