The effect of LNA nucleobases as enhancers for the binding of amiloride to an abasic site in DNA/DNA and DNA/RNA duplexes

We report on a significant effect of locked nucleic acid (LNA) nucleobases on the binding of amiloride for abasic site (AP)-containing DNA duplexes. Fluorescence titration experiments showed that the binding affinity of amiloride for the target thymine (T) opposite an AP site significantly improves for the DNA duplexes possessing LNA nucleobases that flank the AP site, compared to the corresponding normal DNA duplexes. In particular, LNA flanking nucleobases on both 5'- and 3'-sides of the AP site are found to be effective for the enhancement of the binding affinity. From thermodynamic characterization of the amiloride binding, the loss in the binding entropy is remarkably reduced for the LNA-containing DNA duplexes, which is indeed responsible for the enhanced affinity of amiloride. Moreover, such an effect of LNA nucleobases was also observed for amiloride binding to DNA/RNA hybrid duplexes.