Design and examination of potent pseudosubstrate-based oligonucleotide inhibitors against bacterial topoisomerase IV

Abstract

Topoisomerase IV is an enzyme that is mainly responsible for unwinding interlocked DNA strands at the final stage of prokaryotic DNA replication. Due to its exclusivity in prokaryotes, topoisomerase IV has been identified as a validated target for quinolone-based antibiotics in the past years for treating bacterial infection. In consideration that bacterial resistance to such antibiotics has occurred constantly, several newly designed pseudosubstrate oligonucleotides as DNA topoisomerase IV inhibitors have been examined during our recent investigations. Among them, the nick-, gap- and mismatched base pair-containing oligonucleotides displayed significantly high inhibitory effects toward topoisomerase IV. It is our anticipation that the outcomes of our current studies could be beneficial for the future development of pseudosubstrate-based enzyme inhibitors as well as new types of antibiotics.