XNA (xylo nucleic acid):: A summary and new derivatives

被引：29

作者：

Babu, BR ^{[1
]}

Raunak

Poopeiko, NE

Juhl, M

Bond, AD

Parmar, VS

Wengel, J

机构：

[1] Univ So Denmark, Nucle Acid Ctr, Dept Chem, DK-5230 Odense, Denmark

[2] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India

[3] Univ Copenhagen, Dept Chem, DK-2100 Copenhagen, Denmark

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 2005卷 / 11期

关键词：

xylo nucleic acid (XNA); 2 '-deoxy-xylo nucleic acid (dXNA); locked nucleic acid; triple helix; preferential RNA hybridization; xylo-clamp;

D O I：

10.1002/ejoc.200500023

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Fully modified homopyrimidine 2 '-deoxy-xylo nucleic acid (dXNA) form triple helixes with complementary DNA/RNA with thermal stabilities comparable to those of the corresponding DNA:DNA and DNA:RNA duplexes. However, a single or few insertions of dXNA monomers in a DNA strand significantly lower duplex stabilities. The dXNA monomers are known to adopt predominantly an N-type furanose conformation in solution. With a desire to increase the binding affinity, seven sugar-modified XNA monomers (H, F, N, M, K, P and O) have been synthesised and their effect on hybridization towards DNA and RNA complements studied. The introduction of 2 '-fluoro and 2 '-hydroxy substituents was expected to induce conformational restriction towards C3 '-endo-type furanose conformation of monomer F derived from 1-(2 '-deoxy-2 '-fluoro-beta-D-xylofuranosyl)thymine and monomer H derived from 1-(P-D-xylofuranosyl)thymine. The presence of functionalites facing the minor groove as in 1-(2 ' amino-2 '-deoxy-2 '-N,4 '-C-methylene-beta-D-xylofuranosyl)thymine (monomer N), 1-[4-C-(N-methylpiperazinyl)methyl-beta-D-xylofuranosyl]thymine (monomer P), 1-(4-C-piperazinylmethyl-beta-D-xylofuranosyl)thymine (monomer Q), 1-(4-C-hydroxymethyl-beta-D-xylofuranosyl)thymine (monomer M) and 9-(4-C-hydroxymethyl-beta-D-xylofuranosyl) adenine (monomer K) was studied, with monomer N being locked in an N-type furanose conformation. Besides, an efficient synthesis of known xylo-LNA phosphoramidite 19, required for the incorporation of 1-(2 '-0,4 '-C-methylene-beta-D-xylofuranosyl)thymine (monomer L) is described. For comparison, hydridization data of various XNAs reported in the literature are included in the discussion section. The thermal denaturation studies show that XNAs containing conformationally locked monomers (N and L) display improved binding affinity, and that partially modified DNA/XNA chimera, or fully modified XNA display preferential hybridization towards RNA complements. (c) Wiley-VCH Verlag GmbH & Co.

引用

页码：2297 / 2321

页数：25

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