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

In order to develop novel antigene molecules forming thermally stable triplexes with target DNAs and having nuclease resistance properties, e synthesized oligodeoxynucleotides (ODNs) with various lengths of aminoalkyl-linkers at the 4'alpha position of thymidine and the aminoethyl-linker at the 4'alpha 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-tinker or the nucleoside 3 with the aminopropyl-linker thermally stabilized the triplexes, whereas the ODNs containing the nucleoside I 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'alpha-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 all 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'alpha-C-(2-aminoethyl)-2'-deoxynucleosides were good candidates for antigene molecules. (C) 2002 Elsevier Science Ltd. All rights reserved.