Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/126311
Title: Solvation-guided design of fluorescent probes for discrimination of amyloids
Author: Cao, Kevin J.
Elbel, Kristyna M.
Cifelli, Jessica L.
Cirera Fernández, Jordi
Sigurdson, Christina J.
Paesani, Francesco
Theodorakis, Emmanuel A.
Yang, Jerry
Keywords: Malalties neurodegeneratives
Proteïnes
Amiloïdosi
Neurodegenerative diseases
Proteins
Amyloidosis
Issue Date: 3-May-2018
Publisher: Nature Publishing Group
Abstract: The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often 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 ab initio 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's-related beta-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.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41598-018-25131-2
It is part of: Scientific Reports, 2018, vol. 8, p. 6950
URI: http://hdl.handle.net/2445/126311
Related resource: https://doi.org/10.1038/s41598-018-25131-2
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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