title: A detective story in drug discovery: elucidation of a screening artifact reveals polymeric carboxylic acids as potent inhibitors of RNA polymerase.
abstract: Chasing the active impurity: In the validation of a screening hit it was discovered that a polymeric trace impurity was responsible for the biological activity. Such a side product can be formed with similar compounds. During the investigations it was discovered that the negatively charged macromolecule interacts very efficiently with the protein surface of E. coli RNAP via electrostatic interactions.
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland and Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhu
authors.forename: Matthias
authors.initials: M
authors.lastname: Groh
authors.forename: Jörg
authors.initials: J
authors.lastname: Haupenthal
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D004247:DNA; D012321:DNA-Directed RNA Polymerases