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While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits\u00a0often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with <jats:italic>ab initio<\/jats:italic> computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer\u2019s-related \u03b2-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment.<\/jats:p>","DOI":"10.1038\/s41598-018-25131-2","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T09:05:54Z","timestamp":1524819954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Solvation-Guided Design of Fluorescent Probes for Discrimination of Amyloids"],"prefix":"10.1038","volume":"8","author":[{"given":"Kevin J.","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristyna M.","family":"Elbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Cifelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Cirera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina J.","family":"Sigurdson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paesani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-6919","authenticated-orcid":false,"given":"Emmanuel A.","family":"Theodorakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-7376","authenticated-orcid":false,"given":"Jerry","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"key":"25131_CR1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.jalz.2015.02.003","volume":"11","author":"Alzheimer\u2019s Association.","year":"2015","unstructured":"Alzheimer\u2019s Association. 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