Oligoribonucleotides containing 2′,5′-phosphodiester linkages exhibit binding selectivity for 3′,5′-RNA over 3′,5′-ssDNA

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Abstract
Oligoribonucleotides containing 2′,5′-phosphodiester linkages have been synthesized on a solid support by the ′silyl-phosphoramidite′ method. The stability of complexes formed between these oligonucleotides and complementary 3′,5′-RNA strands have been studied using oligoadenylates and a variety of oligonucleotides of mixed base sequences including phosphorothioate backbones. In many cases, particularly for 2′,5′-linked adenylates, the UV melting profiles are quite sharp and exhibit large hyperchromic changes. Substituting a few 3′,5′-linkages with the 2′,5′-linkage within an oligomer lowers the Tm of the complex and the degree of destabilization depends on the neighboring residues and neighboring linkages. The 2′,5′-linked oligoribonucleotides prepared in this study exhibited remarkable selectivity for complementary single stranded RNA over DNA. For example, in 0.01 M phosphate buffer − 0.10 M NaCI (pH 7.0), no association was observed between 2,5′-r(CCC UCU CCC UUC U) and its Watson-Crick DNA complement 3′,5′-d(AGAAGGGAGAGGG). However, 2′,5′-r(CCC UCU CCC UUC U) with its RNA complement 3′,5′-r(AGAAGGGAGAGGG) forms a duplex which melts at 40˚C. The decamer 2′,5′-r(Ap)9A forms a complex with both poly dT and poly rU but the complex [2′,5′-r(Ap)9A]:[poly dT] is unstable (Tm, − 1˚C) and is seen only at high salt concentrations. In view of their unnatural character and remarkable selectivity for single stranded RNA, 2′,5′-oligo-RNAs and their derivatives may find use as selective inhibitors of viral mRNA translation, and as affinity ligands for the purification of cellular RNA.

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