Detection and prevention of aggregation-based false positives in STD-NMR-based fragment screening

Amelia Vom, Stephen James Headey, Geqing Wang, Benvenuto Capuano, Elizabeth Yuriev, Martin Scanlon, Jamie Scott Simpson

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Aggregation of small organic compounds is a problem encountered in a variety of assay screening formats where it often results in detection of false positives. A saturation transfer difference-NMR-detected screen of a commercially available fragment library, followed by biochemical assay, identified several inhibitors of the enzyme ketopantoate reductase. These inhibitors were subsequently revealed to be aggregation-based false positives. Modification of the fragment screen by addition of detergent in the saturation transfer difference-NMR experiments allowed an assay format to be developed that resulted in the identification of genuine hit molecules suitable for further development.
Original languageEnglish
Pages (from-to)1518 - 1524
Number of pages7
JournalAustralian Journal of Chemistry
Volume66
Issue number12
DOIs
Publication statusPublished - 2013

Cite this

Vom, Amelia ; Headey, Stephen James ; Wang, Geqing ; Capuano, Benvenuto ; Yuriev, Elizabeth ; Scanlon, Martin ; Simpson, Jamie Scott. / Detection and prevention of aggregation-based false positives in STD-NMR-based fragment screening. In: Australian Journal of Chemistry. 2013 ; Vol. 66, No. 12. pp. 1518 - 1524.
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Detection and prevention of aggregation-based false positives in STD-NMR-based fragment screening. / Vom, Amelia; Headey, Stephen James; Wang, Geqing; Capuano, Benvenuto; Yuriev, Elizabeth; Scanlon, Martin; Simpson, Jamie Scott.

In: Australian Journal of Chemistry, Vol. 66, No. 12, 2013, p. 1518 - 1524.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Detection and prevention of aggregation-based false positives in STD-NMR-based fragment screening

AU - Vom, Amelia

AU - Headey, Stephen James

AU - Wang, Geqing

AU - Capuano, Benvenuto

AU - Yuriev, Elizabeth

AU - Scanlon, Martin

AU - Simpson, Jamie Scott

PY - 2013

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AB - Aggregation of small organic compounds is a problem encountered in a variety of assay screening formats where it often results in detection of false positives. A saturation transfer difference-NMR-detected screen of a commercially available fragment library, followed by biochemical assay, identified several inhibitors of the enzyme ketopantoate reductase. These inhibitors were subsequently revealed to be aggregation-based false positives. Modification of the fragment screen by addition of detergent in the saturation transfer difference-NMR experiments allowed an assay format to be developed that resulted in the identification of genuine hit molecules suitable for further development.

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U2 - 10.1071/CH13286

DO - 10.1071/CH13286

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SP - 1518

EP - 1524

JO - Australian Journal of Chemistry

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