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Catechol-Containing Compounds are a Broad Class of Amyloid Inhibitors: I. Redox State is a Key Determinant of the Activities of the Inhibitory Activities
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.10.08.873620v1?rss=1
Authors: Velander, P., Wu, L., Hildreth, S. B., Vogelaar, N. J., Mukhopadhyay, B., Zhang, S., Helm, R. F., Xu, B.
Abstract:
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, 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 inhibitors is a key determinant of the amyloid inhibitor activities.
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By Multimodal LLCLink to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.10.08.873620v1?rss=1
Authors: Velander, P., Wu, L., Hildreth, S. B., Vogelaar, N. J., Mukhopadhyay, B., Zhang, S., Helm, R. F., Xu, B.
Abstract:
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, 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 inhibitors is a key determinant of the amyloid inhibitor activities.
Copy rights belong to original authors. Visit the link for more info