(2′-O-Methyl-RNA)-3′-PNA Chimeras: A New Class of Mixed Backbone Oligonucleotide Analogues with High Binding Affinity to RNA
The automated on‐line synthesis of DNA‐3′‐PNA chimeras 1–4 and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras 5–8 is described, in which the 3′‐terminal part of the oligonucleotide is linked to the N‐terminal part of the PNA via N‐(ω‐hydroxyalkyl)‐N‐[(thymin‐1‐yl)acetyl]glycine units (alkyl=Et, Ph, Bu, and penty...
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Published in | Helvetica chimica acta Vol. 85; no. 9; pp. 2619 - 2626 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Basel
WILEY-VCH Verlag
01.09.2002
WILEY‐VCH Verlag Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | The automated on‐line synthesis of DNA‐3′‐PNA chimeras 1–4 and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras 5–8 is described, in which the 3′‐terminal part of the oligonucleotide is linked to the N‐terminal part of the PNA via N‐(ω‐hydroxyalkyl)‐N‐[(thymin‐1‐yl)acetyl]glycine units (alkyl=Et, Ph, Bu, and pentyl). By means of UV thermal denaturation, the binding affinities of all chimeras were directly compared by determining their Tm values in the duplex with complementary DNA and RNA. All investigated DNA‐3′‐PNA chimeras and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras form more‐stable duplexes with complementary DNA and RNA than the corresponding unmodified DNA. Interestingly, a N‐(3‐hydroxypropyl)glycine linker resulted in the highest binding affinity for DNA‐3′‐PNA chimeras, whereas the (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras showed optimal binding with the homologous N‐(4‐hydroxybutyl)glycine linker. The duplexes of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras and RNA were significantly more stable than those containing the corresponding DNA‐3′‐PNA chimeras. Surprisingly, we found that the charged (2′‐O‐methyl‐RNA)‐3′‐PNA chimera with a N‐(4‐hydroxybutyl)glycine‐based unit at the junction to the PNA part shows the same binding affinity to RNA as uncharged PNA. Potential applications of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras include their use as antisense agents acting by a RNase‐independent mechanism of action, a prerequisite for antisense‐oligonucleotide‐mediated correction of aberrant splicing of pre‐mRNA. |
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Bibliography: | istex:0665589F8E896ECF0A64348E1F5ECDB9F9AC1E80 ark:/67375/WNG-85SRZX1P-X ArticleID:HLCA2619 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0018-019X 1522-2675 |
DOI: | 10.1002/1522-2675(200209)85:9<2619::AID-HLCA2619>3.0.CO;2-7 |