Deconvoluting binding sites in amyloid nanofibrils using time-resolved spectroscopy

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dc.citation.firstpage1072en_US
dc.citation.journalTitleChemical Scienceen_US
dc.citation.lastpage1081en_US
dc.citation.volumeNumber14en_US
dc.contributor.authorJiang, Boen_US
dc.contributor.authorUmezaki, Utanaen_US
dc.contributor.authorAugustine, Andreaen_US
dc.contributor.authorJayasinghe-Arachchige, Vindi M.en_US
dc.contributor.authorSerafim, Leonardo F.en_US
dc.contributor.authorHe, Zhi Mei Soniaen_US
dc.contributor.authorWyss, Kevin M.en_US
dc.contributor.authorPrabhakar, Rajeeven_US
dc.contributor.authorMartí, Angel A.en_US
dc.date.accessioned2023-02-23T18:46:11Zen_US
dc.date.available2023-02-23T18:46:11Zen_US
dc.date.issued2023en_US
dc.description.abstractSteady-state fluorescence spectroscopy has a central role not only for sensing applications, but also in biophysics and imaging. Light switching probes, such as ruthenium dipyridophenazine complexes, have been used to study complex systems such as DNA, RNA, and amyloid fibrils. Nonetheless, steady-state spectroscopy is limited in the kind of information it can provide. In this paper, we use time-resolved spectroscopy for studying binding interactions between amyloid-β fibrillar structures and photoluminescent ligands. Using time-resolved spectroscopy, we demonstrate that ruthenium complexes with a pyrazino phenanthroline derivative can bind to two distinct binding sites on the surface of fibrillar amyloid-β, in contrast with previous studies using steady-state photoluminescence spectroscopy, which only identified one binding site for similar compounds. The second elusive binding site is revealed when deconvoluting the signals from the time-resolved decay traces, allowing the determination of dissociation constants of 3 and 2.2 μM. Molecular dynamic simulations agree with two binding sites on the surface of amyloid-β fibrils. Time-resolved spectroscopy was also used to monitor the aggregation of amyloid-β in real-time. In addition, we show that common polypyridine complexes can bind to amyloid-β also at two different binding sites. Information on how molecules bind to amyloid proteins is important to understand their toxicity and to design potential drugs that bind and quench their deleterious effects. The additional information contained in time-resolved spectroscopy provides a powerful tool not only for studying excited state dynamics but also for sensing and revealing important information about the system including hidden binding sites.en_US
dc.identifier.citationJiang, Bo, Umezaki, Utana, Augustine, Andrea, et al.. "Deconvoluting binding sites in amyloid nanofibrils using time-resolved spectroscopy." <i>Chemical Science,</i> 14, (2023) Royal Society of Chemisty: 1072-1081. https://doi.org/10.1039/D2SC05418C.en_US
dc.identifier.digitald2sc05418cen_US
dc.identifier.doihttps://doi.org/10.1039/D2SC05418Cen_US
dc.identifier.urihttps://hdl.handle.net/1911/114475en_US
dc.language.isoengen_US
dc.publisherRoyal Society of Chemistyen_US
dc.rightsThis Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licenceen_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.titleDeconvoluting binding sites in amyloid nanofibrils using time-resolved spectroscopyen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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