No Compromises, Native Molecule Drug Discovery Assays Using Mass

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Recently there has been increased interest in screening chemical libraries for non-covalent or covalent binding to RNA or protein drug discovery targets using native conditions. Solution phase binding with native targets and test compounds avoids potential compromises inherent to assays based on labeled or immobilized components. In this webinar, we will describe simple, automated, and high throughput workflows utilizing mass spectrometry (MS) to measure drug candidate binding. Two workflows will be described in detail: 1) non-covalent/reversible binding by Affinity Selection Mass Spectrometry (ASMS) and 2) covalent/irreversible binding by intact mass shift assays. Both methodologies facilitate the efficient interrogation of large data sets in a high-throughput manner followed by further hit candidate characterization. These MS-based assay methods are applicable to many different classes of targets and therapeutic areas, for example: RNA and protein degraders, RNA as a novel drug target, molecular glues and protein-protein interactions. Some of the advantages of this methodology over other drug target binding assay methods are minimal target quantity and assay development is required, protocol flexibility, target versatility, and primary hits are immediately identified and available for further confirmation and follow-up experiments (i.e., Kinact/Ki measurements, peptide mapping, quantitative proteomics, etc.). Key Learning Objectives: Understand how and when to use the ASMS & intact mass shift workflows for drug discovery screening Learn about the advantages of native molecule mass spectrometry binding assays versus other methodologies Learn how to utilize mass spectrometry for hit follow-up confirmation and characterization