Automation of a Generic Fluorescence Methyltransferase Activity Assay

Methylation is known to be a ubiquitous covalent modification involved in regulation of a diverse range of biomolecules. Histone methyltransferases (HMTs) are of particular interest as drug targets as histone methylation is linked to certain disease states, including a wide variety of cancer types. A high-throughput screening (HTS)-ready, universal methyltransferase activity assay was recently developed based on competitive fluorescent polarization immunodetection of AMP, formed from the methyltransferase (MT) reaction product S-adenosylhomocysteine in a dual enzyme coupling step. This work demonstrates automation of the assay in a 384-well format suitable for HTS.