A detective story in drug discovery: elucidation of a screening artifact reveals polymeric carboxylic acids as potent inhibitors of RNA polymerase.

Authors :: Zhu W
Groh M
Haupenthal J
Hartmann RW
Source :: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2013 Jun 24; Vol. 19 (26), pp. 8397-400. Date of Electronic Publication: 2013 May 16.
Publication Year :: 2013
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.<br /> (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Subjects :: Carboxylic Acids metabolism
Chromatography, High Pressure Liquid
DNA chemistry
DNA metabolism
DNA-Directed RNA Polymerases isolation & purification
DNA-Directed RNA Polymerases metabolism
Enzyme Inhibitors metabolism
Escherichia coli enzymology
Protein Binding
Protein Structure, Tertiary
Static Electricity
Carboxylic Acids chemistry
DNA-Directed RNA Polymerases antagonists & inhibitors
Enzyme Inhibitors chemistry

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