Journal Article

Novel synthetic molecules targeting the bacterial RNA polymerase assembly

Estelle André, Lionel Bastide, Sylvie Michaux-Charachon, Anne Gouby, Philippe Villain-Guillot, Jaqueline Latouche, Aurélie Bouchet, Maxime Gualtiéri and Jean-Paul Leonetti

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 2, pages 245-251
Published in print February 2006 | ISSN: 0305-7453
Published online December 2005 | e-ISSN: 1460-2091 | DOI:
Novel synthetic molecules targeting the bacterial RNA polymerase assembly

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  • Medical Oncology
  • Critical Care


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Objectives: Despite extensive functional screening of the bacterial RNA polymerase (RNAP) over the past years, very few novel inhibitors have been reported. We have, therefore, decided to screen with a radically different, non-enzymic, protein–protein interaction assay. Our target is the highly conserved RNAP–σ interaction that is essential for transcription.

Methods: Small molecule inhibitors of the RNAP–σ interaction were tested for their activity on transcription and on bacteria.

Results: These compounds have antibacterial activity against Gram-positive bacteria including multiresistant clinical isolates.

Conclusions: This is, to our knowledge, the first example of a small molecule inhibitor of this interaction.

Keywords: transcription; antibacterial drug screening; antibacterials; antibiotic resistance; anti-infective agents

Journal Article.  4108 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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