Nucleosides and nucleotides. Part 214: thermal stability of triplexes containing 4′α- C-Aminoalkyl-2′-deoxynucleosides

Abstract

In order to develop novel antigene molecules forming thermally stable triplexes with target DNAs and having nuclease resistance properties, we synthesized oligodeoxynucleotides (ODNs) with various lengths of aminoalkyl-linkers at the 4′α position of thymidine and the aminoethyl-linker at the 4′α position of 2′-deoxy-5-methylcytidine. Thermal stability of triplexes between these ODNs and a DNA duplex was studied by thermal denaturation. The ODNs containing the nucleoside 2 with the aminoethyl-linker or the nucleoside 3 with the aminopropyl-linker thermally stabilized the triplexes, whereas the ODNs containing the nucleoside 1 with the aminomethyl-linker or the nucleoside 4 with the 2-[ N-(2-aminoethyl)carbamoyl]oxy]ethyl-linker thermally destabilized the triplexes. The ODNs containing 2 were the most efficient at stabilizing the triplexes with the target DNA. The ODNs containing 4′α- C-(2-aminoethyl)-2′-deoxy-5-methylcytidine ( 5) also efficiently stabilized the triplexes with the target DNA. Stability of the ODN containing 5 to nucleolytic hydrolysis by snake venom phosphodiesterase (a 3′-exonuclease) was studied. It was found that the ODN containing 5 was more resistant to nucleolytic digestion by the enzyme than an unmodified ODN. In a previous paper, we reported that the ODNs containing 2 were more resistant to nucleolytic digestion by DNase I (an endonuclease) than the unmodified ODNs. Thus, it was found that the ODNs containing 4′α- C-(2-aminoethyl)-2′-deoxynucleosides were good candidates for antigene molecules.