Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors.

ABSTRACT: Methyltransferases (MTases) play diverse roles in cellular processes. Aberrant methylation levels have been implicated in many diseases, indicating the need for the identification and development of small molecule inhibitors for each MTase. Specific inhibitors can serve as probes to investigate the function and validate therapeutic potential for the respective MTase. High-throughput screening (HTS) is a powerful method to identify initial hits for further optimization. Here, we report the development of a fluorescence-based MTase assay and compare this format with the recently developed MTase-Glo luminescence assay for application in HTS. Using protein N-terminal methyltransferase 1 (NTMT1) as a model system, we miniaturized to 1536-well quantitative HTS format. Through a pilot screen of 1

SUBMITTER: Dong G 

PROVIDER: S-EPMC7429283 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature