Stabilisation of RNA Bulges by Oligonucleotide Complements Containing an Adenosine Analogue

Abstract Incorporation of 2′‐deoxy‐2′‐ β ‐(1‐naphthylmethyl)tubercidin into an oligodeoxyribonucleotide mostly has little or a slightly negative effect on the T m values of complexes with DNA complements. With the same naphthylmethyl‐substituted nucleoside at the 3′‐end of a 2′‐O‐methyloligoribonucleotide, however, a stabilisation of 1–2 °C in the corresponding complexes with both DNA and RNA is observed. When the target sequence is an RNA fragment forming a two‐ or three‐nucleotide bulge, complexes with (naphthylmethyl)tubercidin‐modified oligodeoxyribonucleotides, as well as with the corresponding 2′‐O‐methyloligoribonucleotides, give stabilisations of 1–2 °C for the three‐nucleotide bulge and of almost 4 °C for the two‐nucleotide bulge. This stabilisation is specific to RNA, since the corresponding complexes with the DNA fragments do not display this effect. Thus, the (naphthylmethyl)tubercidin‐containing oligonucleotides are the first reported oligonucleotide modifications that specifically stabilise bulged RNA.