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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
From determinants of RUNX1/ETO tetramerization to small-molecule protein-protein interaction inhibitors targeting
Alexander Metz1, Julia Schanda, Manuel Grez
1Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University , Universitätsstr. 1, 40225 Düsseldorf, Germany.
Abstract:
We identified the first small-molecule protein-protein interaction inhibitors of RUNX1/ETO tetramerization applying structure-based virtual screening guided by predicted hot spots and pockets in the interface. A 3D similarity screening revealed specific hot spot mimetics, one of which prevents the proliferation of RUNX1/ETO-dependent SKNO-1 cells at low micromolar concentration. Using solely a protein-protein complex structure to start with, this strategy can be the first step in any comparable structure-based endeavor to identify protein-protein interaction inhibitors.
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