Bulge oligonucleotide as an inhibitory agent of bacterial topoisomerase I

J Enzyme Inhib Med Chem. 2018 Dec;33(1):319-323. doi: 10.1080/14756366.2017.1419218.

Abstract

Bacterial topoisomerase I (Btopo I) was defined as potential target for discovery of new antibacterial compounds. Various oligonucleotides containing bulge structure were designed and synthesised as inhibitors to Btopo I in this investigation. The results of this study demonstrated that the designed oligonucleotides display high inhibitory efficiency on the activity of Btopo I and the inhibitory effect could be modulated by the amount of bulge DNA bases. The most efficient one among them showed an IC50 value of 63.1 nM in its inhibition on the activity of Btopo I. In addition, our studies confirmed that the designed oligonucleotide would induce irreversible damages to Btopo I and without any effects occur to eukaryotic topoisomerase I. It is our hope that the results provided in these studies could provide a novel way to inhibit Btopo I.

Keywords: Bacterial topoisomerase I; bulge oligonucleotide; inhibitor.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors / chemical synthesis
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Oligonucleotides
  • Topoisomerase I Inhibitors

Grants and funding

We are greatly appreciating National Natural Science Foundation of China (No. 81402843), Fok Ying-Tong Education Foundation (No. 151028), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry for financial support this research work.