Why combining MALDI-MS and PEAs became the perfect assay for “me”

Assay choice is critical for any drug discovery program. Methyltransferase (MTase) enzymes are notoriously challenging due to the diversity of their substrates and that many substrates can achieve higher order methylation states, including Me1, Me2, and even Me3. Legacy assay technologies prefer to measure the metabolism of the SAM cofactor (the methyl donor), which leads to open questions around the achieved methylation state and impact of inhibitors. Developing antibodies to recognize distinct methylation states is challenging given the subtle differences of a single methyl group and the similarities of many substrate sequences. Traditional mass spectrometry can be often slow and restrictive. Our platform combining surface chemistry using polymeric enrichment arrays (PEAs) and state-of-the-art MALDI instrumentation overcomes these limitations with a label-free, direct, and ultra high-throughput readout of MTase activities. Download the case study focused on the protein arginine methyltransferase (PRMT5) enzyme and see how this assay platform is perfectly suited for confidently distinguishing “me” (methyl) groups and characterizing small molecule inhibitors to advance your drug discovery program. .