NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity

Paxton Forgue; Steven Halouska; Mark Werth; Kaimei Xu; Steve Harris; Robert Powers

doi:10.1021/pr060114v

NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity

Paxton Forgue, Steven Halouska, Mark Werth, Kaimei Xu, Steve Harris, Robert Powers

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1916-1923
Number of pages	8
Journal	Journal of proteome research
Volume	5
Issue number	8
DOIs	https://doi.org/10.1021/pr060114v
State	Published - Aug 2006

Keywords

Aspergillus nidulans
Drug discovery
Metabolomics
NMR
Principle component analysis
Purine degradation pathway
Pyrimidine biosynthetic pathway

ASJC Scopus subject areas

Biochemistry
Chemistry(all)

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10.1021/pr060114v

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abstract = "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.",

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T1 - NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity

AU - Forgue, Paxton

AU - Halouska, Steven

AU - Werth, Mark

AU - Xu, Kaimei

AU - Harris, Steve

AU - Powers, Robert

PY - 2006/8

Y1 - 2006/8

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AB - 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.

KW - Aspergillus nidulans

KW - Drug discovery

KW - Metabolomics

KW - NMR

KW - Principle component analysis

KW - Purine degradation pathway

KW - Pyrimidine biosynthetic pathway

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NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity

Abstract

Keywords

ASJC Scopus subject areas

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