Catechol-Containing Compounds are a Broad Class of Amyloid Inhibitors: I. Redox State is a Key Determinant of the Activities of the Inhibitory Activities
Velander, P.; Wu, L.; Hildreth, S. B.; Vogelaar, N. J.; Mukhopadhyay, B.; Zhang, S.; Helm, R. F.; Xu, B.
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Mechanisms 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, A{beta} 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.
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