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Multifunctional molecules, which can target metal-free and metal-bound A\u03b2 and modulate their reactivity (<jats:italic>e.g<\/jats:italic>., A\u03b2 aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free\/-associated A\u03b2 and further control both metal-free and metal-induced A\u03b2 aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound A\u03b2. Of the polyphenols investigated, the natural product (<jats:bold>Verbascoside<\/jats:bold>) and its esterified derivative (<jats:bold>VPP<\/jats:bold>) regulate the aggregation and cytotoxicity of metal-free and\/or metal-associated A\u03b2 to different extents. Our studies indicate<jats:bold>Verbascoside<\/jats:bold>represents a promising structure for further multifunctional tool development against both metal-free A\u03b2 and metal-A\u03b2.<\/jats:p>","DOI":"10.1038\/srep17842","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T10:13:06Z","timestamp":1449742386000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Reactivity of Metal-Free and Metal-Associated Amyloid-\u03b2 with Glycosylated Polyphenols and Their Esterified Derivatives"],"prefix":"10.1038","volume":"5","author":[{"given":"Kyle J.","family":"Korshavn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milim","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Ju","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vertuani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Bhunia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Manfredini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayyalusamy","family":"Ramamoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Hee","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,10]]},"reference":[{"key":"BFsrep17842_CR1","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1002\/anie.200802808","volume":"48","author":"R Jakob-Roetne","year":"2009","unstructured":"Jakob-Roetne, R. & Jacobsen, H. 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