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

dc.contributor.author	Maurer, Christine K
dc.contributor.author	Fruth, Martina
dc.contributor.author	Empting, Martin
dc.contributor.author	Avrutina, Olga
dc.contributor.author	Hoßmann, Jörn
dc.contributor.author	Nadmid, Suvd
dc.contributor.author	Gorges, Jan
dc.contributor.author	Herrmann, Jennifer
dc.contributor.author	Kazmaier, Uli
dc.contributor.author	Dersch, Petra
dc.contributor.author	Müller, Rolf
dc.contributor.author	Hartmann, Rolf W
dc.date.accessioned	2016-08-19T12:59:04Z
dc.date.available	2016-08-19T12:59:04Z
dc.date.issued	2016-06
dc.identifier.citation	Discovery of the first small-molecule CsrA-RNA interaction inhibitors using biophysical screening technologies. 2016, 8 (9):931-47 Future Med Chem	en
dc.identifier.issn	1756-8927
dc.identifier.pmid	27253623
dc.identifier.doi	10.4155/fmc-2016-0033
dc.identifier.uri	http://hdl.handle.net/10033/618599
dc.description.abstract	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).
dc.language.iso	en	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/4.0/	*
dc.title	Discovery of the first small-molecule CsrA-RNA interaction inhibitors using biophysical screening technologies.	en
dc.type	Article	en
dc.contributor.department	German Centre for Infection Research (DZIF), PartnerSite Hannover-Braunschweig, 30625 Hannover, Germany.	en
dc.identifier.journal	Future medicinal chemistry	en
refterms.dateFOA	2017-06-15T00:00:00Z
html.description.abstract	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).