Detection and Prevention of Aggregation-based False Positives in STD-NMR-based Fragment Screening

作者：Vom Amelia; Headey Stephen; Wang Geqing; Capuano Ben; Yuriev Elizabeth; Scanlon Martin J; Simpson Jamie S^*

来源：Australian Journal of Chemistry, 2013, 66(12): 1518-1524.

DOI：10.1071/CH13286

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.

• 出版日期2013