Detection and prevention of aggregation-based false positives in STD-NMR-based fragment screening Academic Article uri icon

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.

authors

  • Vom, A
  • Headey, S
  • Wang, G
  • Capuano, B
  • Yuriev, E
  • Scanlon, MJ
  • Simpson, JS

publication date

  • 2013