Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones.

  title={Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones.},
  author={Heike Br{\"o}tz-Oesterhelt and Igor Knezevic and Stephan Bartel and Thomas Lampe and Ute Warnecke-Eberz and Karl B Ziegelbauer and Dieter Haebich and Harald Labischinski},
  journal={The Journal of biological chemistry},
  volume={278 41},
Pyridochromanones were identified by high throughput screening as potent inhibitors of NAD+-dependent DNA ligase from Escherichia coli. Further characterization revealed that eubacterial DNA ligases from Gram-negative and Gram-positive sources were inhibited at nanomolar concentrations. In contrast, purified human DNA ligase I was not affected (IC50 > 75 microm), demonstrating remarkable specificity for the prokaryotic target. The binding mode is competitive with the eubacteria-specific… CONTINUE READING