An Electrochemical Probe of DNA Stacking in an Antisense Oligonucleotide Containing a C3′-endo-Locked Sugar

The preferred base-stacking orientation of a conformationally constrained nucleotide (3′-endo-locked) within DNA/DNA and DNA/RNA duplexes (see picture) was probed by charge transport through DNA-modified gold electrode surfaces. The conformation of the sugar is seen to sensitively determine the local stacking of the duplex. These results illustrate the utility of DNA-mediated charge transport through DNA-modified surfaces in characterizing small perturbations in DNA stacking and structure.