4′-Alkoxy oligodeoxynucleotides: a novel class of RNA mimics

Abstract

4'-Alkoxy-oligothymidylates were prepared as model compounds to study the influence of a C4'-alkoxy group on hybridisation. The phosphodiester homooligomers (15 units long) containing either a 4'-methoxy or 4'-(2-methoxyethoxy) group were found to display increased hybridisation with both dA(15) and rA(15) complementary counterparts compared to the natural oligothymidylate. In addition, we found their hybridisation behaviour to be similar to that of the regioisomeric 2'-O-methyl-oligothymidylate. The formed complexes (duplexes and triplexes) were studied using UV spectroscopy and polyacrylamide gel electrophoresis (PAGE). Structural background of the hybridization behaviour was examined using NMR and MDS. The favourable hybridisation properties of the 4'-alkoxyoligothymidylates indicated that 4'-alkoxy modified nucleotides are promising compounds for the assembly of chimeric oligonucleotides with tunable properties.

Structural basis for the synergy of 4′- and 2′-modifications on siRNA nuclease resistance, thermal stability and RNAi activity

“…Earlier reports of 4′- C -modified nucleotides, including 4′- C -OMe-2′-deoxynucleotides ( 17 , 18 ) and 2′-F,4′- C -F pyrimidine nucleotides ( 19–21 ) and their incorporation into oligonucleotides support the notion of a preference for a Northern sugar pucker. The thermodynamic stability of RNA duplexes containing such nucleotides is similar to that of the native counterparts ( 21 ).…”

Straightforward Synthesis of Purine 4′-Alkoxy-2′-deoxynucleosides: First Report of Mixed Purine–Pyrimidine 4′-Alkoxyoligodeoxynucleotides as New RNA Mimics

“…9 Two types of sequences were evaluated: DNA-like nonamers featuring two 4′-methoxythymidine units (entries 3, 5, and 7), as well as RNAlike nonamers having two 2′-deoxy-4′-methoxyuridine units instead (entries 4 and 6). All of the studied oligomers enhanced the duplex stability with varied potency.…”

The benchmark of 31P NMR parameters in phosphate: a case study on structurally constrained and flexible phosphate

“…8 As for the nucleic acids, the NMR measurements and calculations highlighted the base pairing, the orientation of the base with respect to the sugar, the structure of the sugar-phosphate/phosphonate backbone in canonical/ modified oligonucleotides aimed at medicinal applications, the oxidative damage of DNA, and the 3D structure of metallo-DNAs including Hg/Ag-mediated base pairs. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The 31 P NMR measurements conveniently employ the 100% natural abundance of the isotope. Recent calculations of the 31 P NMR shifts in organophosphorus compounds differing by hundreds of ppm illustrated the reliability of the theoretical DFT methods.…”