Stabilisation of RNA bulges by oligonucleotide complements containing an adenosine analogue.
Incorporation of 2'-deoxy-2'-beta-(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 degrees 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 degrees C for the three-nucleotide bulge and of almost 4 degrees 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.
Madder
Annemieke
A
Division of Organic and Bioorganic Chemistry, MBB, Scheele Laboratory, Karolinska Institutet, 17177 Stockholm, Sweden.
Ehrl
Robert
R
Strömberg
Roger
R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D012313:RNA; D000241:Adenosine