Nucleosides and Nucleotides. Part 206: Introduction of Lipophilic Groups into 4′α-C-(2-Aminoethyl)thymidine-Containing Phosphodiester Oligodeoxynucleotides and Thermal Stabilities of the Duplexes

Synthesis and properties of the 4′α-C-(2-aminoethyl)thymidine (1)-containing oligodeoxynucleotides (ODNs), which have lipophilic groups such as palmitic acid, oleic acid, and cholesterol at the terminal of the aminoethyl linker of the compound 1, are described. The ODNs were synthesized in a DNA synthesizer by using controlled pore glasses (CPGs) having the 4′α-C-[N-(palmitoyl), N-(oleoyl), and N-(cholesteryloxycarbonyl)aminoethyl]thymidine analogs (9a, b, and c). The stability of the duplexes formed by these ODNs and a complementary DNA 15 or RNA 16 was studied by thermal denaturation. It was found that the bulky functional group such as cholesterol thermally destabilizes the DNA/DNA duplexes, but that such thermal destabilization can be offset by the effects of the aminoethyl linker of 1. Furthermore, these lipophilic groups do not largely influence the thermal stability of the DNA/RNA duplexes.