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Establishment of an NMR Workflow to Identify and Validate MutSβ and/or MutSβ-DNA Binding Inhibitors

IRBM poster 26003, preview
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DNA mismatch repair (MMR) helps preserve genome integrity, but it also drives somatic triplet-repeat expansion in Huntington’s disease, making the MutSβ (MSH2–MSH3) complex a relevant target to modulate somatic instability. This poster presents an integrated workflow combining NMR with LC-SEC and LC-HRMS to assess full-length human MutSβ stability in solution, characterize ligand interactions, and confirm both non-covalent and covalent hit engagement while providing early binding-site contact insights to support SAR-driven optimization. It also outlines an NMR-enabled strategy to triage compounds for their ability to block or disrupt MutSβ–DNA complex formation, establishing assay benchmarks even when initial tool compounds do not inhibit this high-affinity interaction. Download the poster to explore the assay cascade and validation/triage logic in detail.

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