Synthesis and properties of 2′-O,4′-C-Ethylene-Bridged nucleic acids (ENA) as effective antisense oligonucleotides

2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) as Next-Generation Antisense and Antigene Agents

“…13,14) The conformational analysis of 2Ј-O,4Ј-C-ethylene nucleosides by 1 H-NMR has shown that in all 2Ј-O,4Ј-C-ethylene nucleosides, the coupling constant (J H1Ј-H2Ј ) was 0 Hz, which was identical to that of 2Ј-O,4Ј-Cmethylene nucleosides. 14) This means that the furanose puckering of 2Ј-O,4Ј-C-ethylene nucleosides are all fixed in the C3Ј-endo conformation (Fig. 2, g).…”

“…Similar results have been obtained by X-ray crystal structure analysis of the 2Ј-O,4Ј-Cethylene nucleosides, which show typical C3Ј-endo conformations. 14,15) The difference between 2Ј-O,4Ј-C-ethylene nucleosides and 2Ј-O,4Ј-C-methylene nucleosides appear clearly in the d torsion angle of C5Ј-C4Ј-C3Ј-O3Ј (Fig. 2, f, g), which is one of the defining angles of the ribose conformation.…”

“…[13][14][15] They also exhibit much higher nuclease-resistance than 2Ј,4Ј-BNA/LNA. [13][14][15] Here, we review the properties of 2Ј-O,4Ј-C-ethylenebridged nucleic acids (ENA) having 2Ј-O,4Ј-C-ethylene nucleosides and the application of their oligonucleotides for use as antisense and antigene oligonucleotides.…”

Nuclease resistant methylphosphonate-DNA/LNA chimeric oligonucleotides

“…[10][11][12][13][14][15] Locked nucleic acid (LNA, Fig. 1), which is a conformationally restricted RNA mimic displaying unprecedented binding affinities towards complementary single stranded RNA or DNA, [16][17][18][19] is a promising modification for AON applications, [20][21][22] and is currently being utilized in various genomic technologies. [23][24][25][26] Introduction of consecutive LNA monomers from the 3 0 -end of an AON efficiently protects against 3 0 -exonucleolytic degradation, 16 whereas isolated LNA monomers in DNA/LNA chimeric AONs offer no significant protection.…”

“…[23][24][25][26] Introduction of consecutive LNA monomers from the 3 0 -end of an AON efficiently protects against 3 0 -exonucleolytic degradation, 16 whereas isolated LNA monomers in DNA/LNA chimeric AONs offer no significant protection. 21 To ensure sufficient biostability of DNA/LNA chimeric AONs, the use of phosphorothioate linkages throughout the AON has proven very efficient. 27,28 Methylphosphonate-DNA (MP-DNA, Fig.…”