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

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.