• Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural diversity?

      Weidel, Elisabeth; Negri, Matthias; Empting, Martin; Hinsberger, Stefan; Hartmann, Rolf W (2014)
      In order to identify new scaffolds for drug discovery, surface plasmon resonance is frequently used to screen structurally diverse libraries. Usually, hit rates are low and identification processes are time consuming. Hence, approaches which improve hit rates and, thus, reduce the library size are required.
    • Discovery of the first small-molecule CsrA-RNA interaction inhibitors using biophysical screening technologies.

      Maurer, Christine K; Fruth, Martina; Empting, Martin; Avrutina, Olga; Hoßmann, Jörn; Nadmid, Suvd; Gorges, Jan; Herrmann, Jennifer; Kazmaier, Uli; Dersch, Petra; Müller, Rolf; Hartmann, Rolf W; German Centre for Infection Research (DZIF), PartnerSite Hannover-Braunschweig, 30625 Hannover, Germany. (2016-06)
      CsrA is a global post-transcriptional regulator protein affecting mRNA translation and/or stability. Widespread among bacteria, it is essential for their full virulence and thus represents a promising anti-infective drug target. Therefore, we aimed at the discovery of CsrA-RNA interaction inhibitors. Results & methodology: We followed two strategies: a screening of small molecules (A) and an RNA ligand-based approach (B). Using surface plasmon resonance-based binding and fluorescence polarization-based competition assays, (A) yielded seven small-molecule inhibitors, among them MM14 (IC50 of 4 µM). (B) resulted in RNA-based inhibitor GGARNA (IC50 of 113 µM).