xylo-configured oligonucleotides (XNA, xylo nucleic acids): Synthesis and hybridization studies

Article abstract of DOI:10.1081/NCN-120022822

We report synthesis and high-affinity hybridization of fully modified home-thymine 2′-deoxy and 2′-deoxy-2′-fluoro xylo nucleic acids.

Full text of DOI:10.1081/NCN-120022822

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xylo-Configured Oligonucleotides (XNA, Xylo Nucleic
Acids): Synthesis and Hybridization Studies
Nicolai E. Poopeiko a , Britta M. Dahl b & Jesper Wengel a c
a Nucleic Acid Center , Department of Chemistry , University of Southern Denmark , Odense
M, Denmark
b Department of Chemistry , University of Copenhagen , Copenhagen, Denmark
c Nucleic Acid Center , Department of Chemistry , University of Southern Denmark ,
Campusvej 55, DK-5230, Odense M, Denmark
Published online: 31 Aug 2006.
To cite this article: Nicolai E. Poopeiko , Britta M. Dahl & Jesper Wengel (2003) xylo-Configured Oligonucleotides (XNA, Xylo
Nucleic Acids): Synthesis and Hybridization Studies, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 1147-1149, DOI:
10.1081/NCN-120022822
To link to this article: http://dx.doi.org/10.1081/NCN-120022822
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 1147–1149, 2003
xylo-Configured Oligonucleotides (XNA, Xylo Nucleic Acids):
Synthesis and Hybridization Studies
Nicolai E. Poopeiko,1 Britta M. Dahl,2 and Jesper Wengel1,
*
1Nucleic Acid Center, Department of Chemistry, University of Southern
Denmark, Odense M, Denmark
2Department of Chemistry, University of Copenhagen,
Copenhagen, Denmark
ABSTRACT
We report synthesis and high-affinity hybridization of fully modified home-thy-
mine 20-deoxy and 20-deoxy-20-fluoro xylo nucleic acids.
Key Words: XNA (xylo nucleic acids); Oligonucleotides; Hybridization.
Oligonucleotides containing 30,40-threo-configured phosphodiester backbone
have attracted only limited attention.[1–4] We here report on novel xylo-configured
oligonucleotides (XNA, Xylo Nucleic Acids). 1-(2-Deoxy-2-fluoro-b-d-xylofurano-
syl) thymine was obtained starting from methyl 2-deoxy-2-fluoro-3,5-di-O-benzoyl-
b-d-xylofuranoside[5] via Vorbruggen-type condensation. The xylonucleosides were
¨
transformed into phosphoramidite building blocks 1[1] and 2 (Sch. 1).
ON1 and XNAs ON2–ON5 were synthesized using standard procedures except
for modified coupling conditions as described for xylo-LNA synthesis.[4,6]
*Correspondence: Jesper Wengel, Nucleic Acid Center, Department of Chemistry, University
of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; Fax: +45 66 15 87 80;
E-mail: jwe@chem.sdu.dk.
1147
DOI: 10.1081/NCN-120022822
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1148
Poopeiko, Dahl, and Wengel
Scheme 1. i) AcOH, Ac2O (3.8:1 v=v), conc. H2SO4, 75 min, 97%; ii) silylated thymine,
TMSTf, 1,2-DCE, reflux, 3 h, 73% (a:b ¼ 1:2); iii) NH3, MeOH, 20 h; iv) DMTrCl, pyridine,
20 h, 90%; v) NCCH2CH2OP(Cl)N(i-Pr)2, (i-Pr)2NEt, DCM, 30 min, 81%.
Table 1. Hybridization studies on XNAs ON2-ON5.a
Complementary DNA Complementary RNA
[d(A14)]
[r(A14)]
Tm=ꢀC (DTm vs. ON1) Tm=ꢀC (DTm vs. ON1)
Sequences
ON1 (T14)
33 (Reference)
23 (ꢁ10)
29 (Reference)
25 (ꢁ4)
ON2 (50-T7dxTT6)
ON3 (50-T7FxTT6)
ON4 (50-(dxT)13T)
ON5 (50-(FxT)13T)
23 (ꢁ10)
25 (ꢁ4)
33 (þ=ꢁ0)
38 (þ9)
36 (þ3)
36 (þ7)
aMedium salt buffer (10 mM sodium phosphate, 100 mM sodium chloride,
0.1 mM EDTA, pH 7.0).
Hybridization data are shown in the Table. A strong destabilizing effect of single
incorporations of both XNA monomers is observed towards a DNA complement.
The first data on hybridization of XNAs towards RNA complements are included
in the Table. It is revealed that XNA is a class of molecules able to efficiently target
RNA, and it is noteworthy that the almost fully modified XNAs (ON4 and ON5)
displays significantly increased binding affinity towards RNA compared to the refe-
rence (ON1). We are currently studying the structure of XNA-containing hybrids.
ACKNOWLEDGMENTS
The Danish Research Agency and The Danish National Research Foundation
are thanked for financial support.
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xylo-Configured Oligonucleotides
1149
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