Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo.

@article{Mills2011NovelBN,
  title={Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo.},
  author={Scott D. Mills and Ann E. Eakin and Ed T. Buurman and Joseph V. Newman and Ning Gao and Hoan Huynh and Kenneth D. Johnson and Sushmita D. Lahiri and Adam B Shapiro and Grant Walkup and Wei Yang and Suzanne S. Stokes},
  journal={Antimicrobial agents and chemotherapy},
  year={2011},
  volume={55 3},
  pages={1088-96}
}
DNA ligases are indispensable enzymes playing a critical role in DNA replication, recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial target. A novel class of substituted adenosine analogs was discovered by target-based high-throughput screening (HTS), and these compounds were optimized to render them more effective and selective inhibitors of LigA. The adenosine analogs inhibited the… CONTINUE READING