| Streamlining HTS for Group Transfer Enzymes |
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Presentation: 4C04 Session: Advanced Technology for Drug Discovery - Part 1Karen Kleman-Leyer, Matt Staeben, Thane Westermeyer and Tony Klink, Robert Lowery, BellBrook Labs Presenting Author: Karen Kleman-Leyer, BellBrook Labs - USA Enzymes that catalyze group transfer (GT) reactions comprise a significant fraction of the human proteome and are a rich source of drug targets because of their role in covalent regulatory cycles. Phosphorylation, glycosylation, sulfonation, methylation, and acetylation represent some of the key types of GT reactions that modulate the function of diverse biomolecules. Development of HTS methods for these enzymes has been problematic because of the diversity of acceptor substrates used by different isoforms. BellBrook Labs has developed a novel assay platform called Transcreener™ that relies upon fluorescence detection of the invariant product of a GT reaction; e.g., ADP for kinases. Transcreener™ enables screening of any isoform in a family, with any acceptor substrate, using the same assay reagents. This approach greatly simplifies metabolic profiling of compounds for conjugation and target selectivity profiling across multiple family members. We will describe Transcreener™ assays for glycosyltransferases, protein kinases and sulfotransferases. |