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Catechol-Containing Compounds are a Broad Class of Amyloid Inhibitors: Redox State is a Key Determinant of the Inhibitory Activities

By Paul Velander, Ling Wu, Sherry B. Hildreth, Nancy J. Vogelaar, Biswarup Mukhopadhyay, Shijun Zhang, Richard F. Helm, Bin Xu

Posted 08 Oct 2020
bioRxiv DOI: 10.1101/2020.10.08.873620

Mechanisms of amyloid inhibition remains poorly understood, in part because most protein targets of amyloid assembly are either partially unfolded or intrinsically disordered, which hinders detailed structural characterizations 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 inhibitors is a key determinant of the amyloid inhibitor activities. ### Competing Interest Statement The authors have declared no competing interest.

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