9-(2′-Deoxy-β-D-xylofuranosyl)adenine Building Blocks for Solid-Phase Synthesis and Properties of Oligo(2′-deoxy-xylonucleotides)

The 9-(2′-deoxy-à-D -threo-pentofuranosyl)adenine (=9-(2′-deoxy-à-D -xylofuranosyl)adeninc, xA_d; 2) was protected at its 6-NH₂ group with cither a benzoyl ( 5a ) or a (dimethyfamino)methylidcnc ( 6a ) residue and with a dimethoxytntyl group at 5′-OH ( 5b, 6b ). Compounds 5b and 6b were then converted into the 3′-phosphonates 5c and 6c ; moreover, the 2-cyanoethyl phosphoramidite 6d was synthesized starting from fib. The DNA building blocks were used for solid-phase synthesis of d(xA)₁₂2-A] ( 8 ). The latter was hybridized with d(xT)12-T] (T_m = 35°); in contrast, with d(T₁₂), complex formation was not observed. Moreover, xAd and xTd were introduced into the self-complementary dodccamcr d(G-T-A-G-A-A-T-T-C-T-A-C) ( 12 ) at different positions lo give the oligomcrs 13 – 16 . All oligonucleotides were characterised by temperature-dependent CD and UV spectroscopy, and in addition, 14 by T-jump experiments. From concentration-dependent T_m measurements, the thermodynamic paraneters of the melting as well as the tendency of hairpin formation of the oligonucleotides were deduced. Oligemer 14 was hydrolyzed by snake-venom phosphodiesterase in a discontinuous way implying a fast hydrolysis of unmodified 3′- and 5′-flanks followed by a slow hydrolysis of the remaining modified tetramer. In contrast to this, oligonucleotide 16 was hydrolyzed in a continuous reaction. In both cases, calf-spleen phosphodiesterase hydrolyzed the oligomer only marginally.