NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity.
We describe a general protocol for using comparative NMR metabolomics data to infer in vivo efficacy, specificity and toxicity of chemical leads within a drug discovery program. The methodology is demonstrated using Aspergillus nidulans to monitor the activity of urate oxidase and orotidine-5'-phosphate decarboxylase and the impact of 8-azaxanthine, an inhibitor of urate oxidase. 8-azaxanthine is shown to inhibit A. nidulans hyphal growth by in vivo inactivation of urate oxidase.
Forgue
Paxton
P
Department of Chemistry and Plant Pathology, University of Nebraska-Lincoln, 68588, USA.
Halouska
Steven
S
Werth
Mark
M
Xu
Kaimei
K
Harris
Steve
S
Powers
Robert
R
D000818:Animals; D001233:Aspergillus nidulans / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015195:Drug Design; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism; D014503:Urate Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D005656:Fungal Proteins; D014970:Xanthines; C018221:8-azaxanthine; D014503:Urate Oxidase; D009964:Orotidine-5'-Phosphate Decarboxylase