Arabinonucleic Acid Research Articles

Synthesis of an arabinonucleic acid (tANA)

The introduction of the p-nitrophenylethyl-(NPE) and p-nitrophenylethoxyxarbonyl- (NPEOC) group for amino and hydroxy protection of purine and pyrimidine arabinofuranosides and their interconversion into the corresponding 3′-phosphoramidite building blocks provided very effective starting materials for solid support oligoarabinonucleotide syntheses. A structural analogue of the Phage T5 histidine tRNA consisting of 78 nucleotide units has been synthesized in excellent yield and high purity.

Hybridization properties of oligoarabinonucleotides

3′-Phosphoramidite derivatives of arabinocytidine, arabinoadenosine, and arabinouridine were prepared and used for the solid-phase synthesis of oligoarabinonucleotides (arabinonucleic acid, or ANA). Thermal denaturation analysis and gel mobility shift assays were used to investigate the interaction between ANA and complementary DNA and RNA. In general, the ANA/DNA and ANA/RNA complexes exhibited melting temperatures comparable to those of the corresponding DNA/DNA and DNA/RNA complexes. Thus the inversion of stereochemistry at the C2′ of ribonucleotides does not have a negative effect on interaction with natural sequences. In fact, in complexes with poly dT, oligoarabinoadenylates displayed greater hybridization affinity than oligoriboadenylates. In summary, we observed that (i) ara(Ap)7A interacted favourably with poly rU and poly dT, (ii) ara(Cp)7C formed a stable complex with poly rG; (iii) ara(Up)7U did not bind with complementary poly rA; and (iv) the mixed oligoarabinonucleotide ara(UCU UCC CUC UCC C) formed complexes with complementary DNA and RNA. Hybridization was observed between the phosphorothioatelinked arabinoadenylate ara(Aps)7A and poly rU and poly dT; however, this binding was weaker than that between the phosphorothioate-linked deoxyriboadenylate d(Aps)7A and poly rU and poly dT. Both ara(Aps)7A and its deoxy analog d(Aps)7A displayed significant and similar resistance to digestion by snake venom phosphodiesterase.