Oligonucleotides containing consecutive 2'-deoxyisoguanosine residues: Synthesis, duplexes with parallel chain orientation, and aggregation

The 2'-deoxyisoguanosine phosphonates 3a and 4a and the phosphoramidites 3b and 4b were prepared as building blocks for solid-phase oligonucleotide synthesis. The diphenylcarbamoyl (dpc) residue was introduced as Zero protecting group which stabilizes the N-glycosylic bond against hydrolysis and prevents the molecule from side reactions. The dpc-protected building blocks 4a,b were employed in solid-phase synthesis and were found to be much more efficient than the unprotected compounds 3a,b. Oligonucleotides with alternating (11) or consecutive isoguanine residues (13-15) were synthesized. They form duplexes with parallel chain orientation. The aggregate d(T-4-iG(4)-T-4) (15) containing four consecutive 2'-deoxyisoguanosine is shown to be a tetramer similar to that of d(T-4-G(4)-T-4).