Discovery of Potent Coumarin-Based Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains Using Structure-Based Design

In immunoglobulin light-chain (LC) amyloidosis, transient unfolding or unfolding and proteolysis enable aggregation of LC proteins, causing potentially fatal organ damage. A drug that kinetically stabilizes LCs could suppress aggregation; however, LC sequences are variable and have no natural ligand...

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Veröffentlicht in:	Journal of medicinal chemistry 2021-05, Vol.64 (9), p.6273-6299
Hauptverfasser:	Yan, Nicholas L, Santos-Martins, Diogo, Nair, Reji, Chu, Alan, Wilson, Ian A, Johnson, Kristen A, Forli, Stefano, Morgan, Gareth J, Petrassi, H. Michael, Kelly, Jeffery W
Format:	Artikel
Sprache:	eng
Schlagworte:	Amyloid - chemistry Coumarins - chemistry Crystallography, X-Ray Drug Design High-Throughput Screening Assays Immunoglobulin Light Chains - chemistry Kinetics Models, Molecular Protein Domains Protein Stability - drug effects
Online-Zugang:	Volltext
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