7‐Deazaguanine DNA: Oligonucleotides with hydrophobic or cationic side chains

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(hxy7c7G‐C)4 (12), d(C‐hxy7c7G)4 (13), and d(npey 7c7G‐C)4 (15) as well as of other oligonucleotides (see 22–25; Table 2; hxy = hex‐1‐ynyl, npey = 5‐aminopent‐1‐ynyl). The Tm 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 npey7c7Gd (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.