SYNTHESIS, BASE FAIRING, AND STRUCTURAL TRANSITIONS OF OLIGODEOXYRIBONUCLEOTIDES CONTAINING 8-AZA-2'-DEOXYGUANOSINE

The synthesis of oligonucleotides containing 8-aza-2'-deoxyguanosine ( z(8)G(d); 1) or its N-8-regioisomer z(8)G(d)() (2) instead of 2'-deox yguanosine (G(d)) is described. For this purpose, the NH2 group of 1 a nd 2 was protected with a (dimethylamino)methylidene residue (-->5, 6) , a 4,4'-dimethoxytrityl group was introduced at 5'-OH (--> 7, 8), and the phosphonates 3a and 4 as well as the phosphoramidite 3b were prep ared. These building blocks were used in solid-phase oligonucleotide s ynthesis. The oligonucleotides were characterized by enzymatic hydroly sis and melting curves (T-m values). The thermodynamic data of the oli gomers 12-15 indicate that duplexes were stabilized when 1 was replaci ng G(d). The aggregation of d(T-G-G-G-G-T) (18) was studied by RP18 HP LC, gel electrophoresis and CD spectroscopy and compared with that of oligonucleotides containing an increasing number of z(8)G(d) residues instead of Gd Similarly to [d(C-G)](3) (12a), the hexamer d(C-z(8)G-C- z(8)G-C-G) (14) underwent salt-dependent B-Z transition.