Portion mismatch in duplex oligonucleotides as inhibitors of bacterial topoisomerase I

Abstract

Bacterial topoisomerase I (Btopo I) has been known as a potential target for anti-bacterial therapy. A series of duplex oligonucleotides with different length of mismatch base pairs have been designed as inhibitors to Btopo I. The interactions between these particularly designed oligonucleotides and Btopo I were investigated and the most efficient one among them displayed an IC₅₀ value of 18.1 nM in its inhibition on the activity of Btopo I. Our studies demonstrate that the activity of Btopo I can be diminished by the duplex oligonucleotides containing mismatch base pairs and provide a new avenue to design Btopo I inhibitors for the treatment of bacterial infections.