SYNTHESIS OF A CARBOXAMIDE LINKED T-ASTERISK-T DIMER AND ITS INCORPORATION IN OLIGONUCLEOTIDES

The condensation of 5'-O-protected 3'-O-(2-amino-ethyl)thymidine with dideoxy-1-thyminyl-beta-D-erythro-pentofuranuronic acid gives a TT di mer with representing a 3'-OCH2CH2NHC(O)-4' linkage connecting the t wo pentofuranosyl moieties. The incorporation of this dimer in oligonu cleotide sequences show only moderately lowered T(m) values when hybri dized with a complementary DNA relative to the unmodified DNA duplex. Consistently, no looped-out or bubble-type structure could be detected in DNA duplexes with an internal TT module. Moreover, the 5-atom car boxamide linker causes complete stop on DNA polymerization and on exon uclease III degradation.