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A Detective Story in Drug Discovery: Elucidation of a Screening Artifact Reveals Polymeric Carboxylic Acids as Potent Inhibitors of RNA Polymerase
Author(s) -
Zhu Weixing,
Groh Matthias,
Haupenthal Jörg,
Hartmann Rolf W.
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201301289
Subject(s) - artifact (error) , drug discovery , trace (psycholinguistics) , computational biology , chemistry , impurity , combinatorial chemistry , polymerase , macromolecule , computer science , nanotechnology , biochemistry , biology , dna , organic chemistry , materials science , artificial intelligence , philosophy , linguistics
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.