Surface plasmon resonance--more than a screening technology: insights in the binding mode of σ70:core RNAP inhibitors.
| Autor: | Hüsecken K; Department of Drug Design & Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C2.3, D-66123 Saarbrücken, Germany., Hinsberger S, Elgaher WA, Haupenthal J, Hartmann RW |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Future medicinal chemistry [Future Med Chem] 2014 Sep; Vol. 6 (14), pp. 1551-65. |
| DOI: | 10.4155/fmc.14.105 |
| Abstrakt: | Aim: Antibiotic resistance has become a major health problem. The σ(70):core interface of bacterial RNA polymerase is a promising drug target. Recently, the coiled-coil and lid-rudder-system of the β' subunit has been identified as an inhibition hot spot. Materials & methods & Results: By using surface plasmon resonance-based assays, inhibitors of the protein-protein interaction were identified and competition with σ(70) was shown. Effective inhibition was verified in an in vitro transcription and a σ(70):core assembly assay. For one hit series, we found a correlation between activity and affinity. Mutant interaction studies suggest the inhibitors' binding site. Conclusion: Surface plasmon resonance is a valuable technology in drug design, that has been used in this study to identify and evaluate σ(70):core RNA polymerase inhibitors. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|