Portion mismatch in duplex oligonucleotides as inhibitors of bacterial topoisomerase I†
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.