Investigations into the binding of jadomycin DS to human topoisomerase IIβ by WaterLOGSY NMR spectroscopy

The jadomycins are a family of secondary metabolites produced by S. venezuelae ISP5230. Specific jadomycins have been shown to possess a variety of anticancer, antifungal, and antibacterial properties, with different molecular mechanisms of action. Herein we demonstrate qualitative and quantitative...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2015-01, Vol.13 (41), p.10324-10327
Main Authors: Martinez-Farina, Camilo F, McCormick, Nicole, Robertson, Andrew W, Clement, Helen, Jee, Alison, Ampaw, Anna, Chan, Nei-Li, Syvitski, Ray T, Jakeman, David L
Format: Article
Language:English
Subjects:
Binding Sites
DNA Topoisomerases, Type II - chemistry
DNA Topoisomerases, Type II - metabolism
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Humans
Isoquinolines - chemistry
Magnetic Resonance Spectroscopy
Molecular Conformation
Stereoisomerism
Water - chemistry
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Summary:The jadomycins are a family of secondary metabolites produced by S. venezuelae ISP5230. Specific jadomycins have been shown to possess a variety of anticancer, antifungal, and antibacterial properties, with different molecular mechanisms of action. Herein we demonstrate qualitative and quantitative direct binding between the validated anticancer target human topoisomerase IIβ and jadomycin DS using WaterLOGSY NMR spectroscopy. Additionally, we report for the first time, that jadomycin DS also binds a variety of other proteins, likely in a non-specific manner. Such interactions may rationalize the potential polypharmacology of jadomycin DS.
ISSN:1477-0520
1477-0539
DOI:10.1039/c5ob01508a