1-(2'-Deoxy-β-D-xylofuranosyl)thymine Building Blocks for Solid-Phase Synthesis and Properties of Oligo(2'-Deoxyxylonucleotides)

Article abstract of DOI:10.1002/hlca.19910740408

1-(2'-Deoxy-β-D-threo-pentafuranosyl)thymine (= 1-(2'-deoxy-β-D-xylofuranosyl)thymine; xT_d; 2) was converted into its phosphonate 3b as well as its 2-cyanoethyl phosphoramidite 3c.Both compounds were used for solid-phase synthesis of d<(xT)12-T> (5), representing the first DNA fragment build up from 3'-5'-linked 2'-deoxy-β-D-xylonucleosides.Moreover, xT_d was introduced into the innermost part of the self-complementary dodecamer d(G-T-A-A-xT-xT-C-T-A-C)2 (9).The CD spectrum of d<(xT)12-T> (5) exhibits reversed Cotton effects compared to d(T12) (6; see Fig.1), implying a left-handed single strand.With d(A12) (7) it could be hybridized to form a propably left-handed double strand d(A12)*d<(xT)12-T> (7*5) which was confirmed by melting experiments in combination with temperature-dependent CD spectroscopy.While 5 was hydrolyzed by snake-venom phosphodiesterase, it was resistant towards calf-spleen phosphodiesterase.The modified, self-complementary duplex 9 was hydrolyzed completely by snake-venom phosphodiesterase, at a twelvefold slower rate compared to unmodified 8; calf-spleen phosphodiesterase hydrolyzed 9 only partially.