Kinetic study of the binding of triplex-forming oligonucleotides containing partial cationic modifications to double-stranded DNA

Article abstract of DOI:10.1016/j.bmcl.2014.05.031

Several triplex-forming oligonucleotides (TFOs) partially modified with 2′-O-(2-aminoethyl)- or 2′-O-(2-guanidinoethyl)-nucleotides were synthesized and their association rate constants (k_on) with double-stranded DNA were estimated by UV spectrophotometry. Introduction of cationic modifications in the 5′-region of the TFOs significantly increased the k_on values compared to that of natural TFO, while no enhancement in the rate of triplex DNA formation was observed when the modifications were in the middle and at the 3′-region. The k_on value of a TFO with three adjacent cationic modifications at the 5′-region was found to be 3.4 times larger than that of a natural one. These results provide useful information for overcoming the inherent sluggishness of triplex DNA formation.