Catechol-Containing Compounds are a Broad Class of Amyloid Inhibitors: Redox State is a Key Determinant of the Inhibitory Activities
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ABSTRACTMechanisms of amyloid inhibition remains poorly understood, in part because most protein targets of amyloid assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization of protein-inhibitor complexes and structural-based mechanistic elucidation. Herein we employed a small molecule screening approach to identify inhibitors against three prototype amyloidogenic proteins: amylin, Aβ and tau. One remarkable class of inhibitors identified was catechol-containing compounds and redox-related quinones/anthraquinones. Further mechanistic studies determined that the redox state of the broad class of catechol-containing compounds is a key determinant of the amyloid inhibitor activities.
2020 ◽
1990 ◽
Vol 265
(8)
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pp. 4583-4591
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2021 ◽
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