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XNA ( xylo Nucleic Acid): A Summary and New Derivatives
Author(s) -
Ravindra Babu B.,
Poopeiko Nicolai E.,
Juhl Martin,
Bond Andrew D.,
Parmar Virinder S.,
Wengel Jesper
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500023
Subject(s) - thymine , furanose , monomer , chemistry , nucleic acid , dna , stereochemistry , nucleic acid analogue , rna , biochemistry , nucleic acid thermodynamics , organic chemistry , ring (chemistry) , polymer , base sequence , gene
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 Q ) 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‐β‐ D ‐xylofuranosyl)thymine and monomer H derived from 1‐(β‐ D ‐xylofuranosyl)thymine. The presence of functionalites facing the minor groove as in 1‐(2'‐amino‐2'‐deoxy‐2'‐ N ,4'‐ C ‐methylene‐β‐ D ‐xylofuranosyl)thymine (monomer N ), 1‐[4‐ C ‐( N ‐methylpiperazinyl)methyl‐β‐ D ‐xylofuranosyl]thymine (monomer P ), 1‐(4‐ C ‐piperazinylmethyl‐β‐ D ‐xylofuranosyl)thymine (monomer Q ), 1‐(4‐ C ‐hydroxymethyl‐β‐ D ‐xylofuranosyl)thymine (monomer M ) and 9‐(4‐ C ‐hydroxymethyl‐β‐ 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'‐ O ,4'‐ C ‐methylene‐β‐ 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)