7-deazaguanine DNA: Oligonucleotides with hydrophobic or cationic side chains

Abstract

The phosphoramidites 6b and 9 as well as the phosphonate 6a derived from 7-(hex-1-ynyl) and 7-[5-(trifluoroacetamido)pent-1-ynyl]-substituted 7-deaza-2'-deoxyguanosines 1 and 10, respectively, were prepared (Scheme 1). They were employed in solid-phase oligodeoxynucleotide synthesis of the alternating octamers d(hxy(7)c(7)G-C)(4) (12), d(C-hxy(7)c(7)G)(4) (13), and d(npey(7)c(7)G-C)(4) (15) as well as of other oligonucleotides (see 22-25; Table 2; hxy = hex-1-ynyl, npey = 5-aminopent-1-ynyl), The T-m values and the thermodynamic data of duplex formation were determined and correlated with the major-groove modification of the DNA fragments. A hexynyl side chain introduced into the 7-position of a 7-deazaguanine residue (see 1) was found to fit into the major groove without any protrusion. The incorporation of the (5-aminopent-1-ynyl)-modified 7-deaza-2'-deoxyguanosine 2 into single-stranded oligomers of the type 24 and 25 did not lead to change in duplex stability compared to the parent oligonucleotides. The self-complementary oligomer 15 with alternating npey(7)c(7)G(d) (2) and dC units did not lead to a cooperative melting, either due to orientational disorder or interaction of the 5-aminopent-1-ynyl moiety with a base or with phosphate residues nearby or on the opposite strand.