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Analysis of Amyloid Beta Aggregation Kinetics Using Sym‐Triazine β‐Sheet Inhibitors
Author(s) -
Veloso Anthony J.,
Hung Vinci W. S.,
Cheng Xin R.,
Kerman Kagan
Publication year - 2012
Publication title -
electroanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 128
eISSN - 1521-4109
pISSN - 1040-0397
DOI - 10.1002/elan.201200216
Subject(s) - fibril , chemistry , biophysics , kinetics , amyloid (mycology) , triazine , nucleation , cyclic voltammetry , in vitro , redox , amyloid beta , electrochemistry , peptide , biochemistry , electrode , polymer chemistry , inorganic chemistry , biology , organic chemistry , physics , quantum mechanics
Abstract AD (Alzheimer’s disease) is a progressive neurodegenerative disorder characterized by the cerebral accumulation of fibrillar amyloid‐beta (Aβ) aggregates. Here we present the electrochemistry of two novel sym‐triazine derivatives (TAE‐1, TAE‐2) as modulators of Aβ 1–42 aggregation in vitro. Incubation studies conducted at physiological conditions demonstrated strong inhibition of β‐sheet fibril formation. Uniquely, square‐wave voltammetry indicated progressive changes in the surface‐availability of amyloid‐intercalated triazines for oxidation, mediated by competing peptide self‐assembly. Time‐resolved voltammetric analysis showed increasing anodic peak currents (≥3‐fold) and progressive shifts in redox potentials, measured over 24 h. The more potent aggregation modulator (TAE‐2) showed prolonged association during the pre‐nucleation states of Aβ.