168696-01-3Relevant academic research and scientific papers
Oligonucleotides Composed of 2′-Deoxy-1′,5′-anhydro-D-mannitol Nucleosides with a Purine Base Moiety
Hossain, Nafizal,Wroblowski, Berthold,Van Aerschot, Arthur,Rozenski, Jef,De Bruyn, Andre,Herdewijn, Piet
, p. 1574 - 1582 (2007/10/03)
2′-Deoxy-D-mannitol nucleosides with a purine base moiety have been conveniently synthesized starting from 1,5-anhydro-4,6-O-benzylidene-D-glucitol. The 3-OH function of 1,5-anhydro-4,6-O-benzylidene-D-glucitol was selectively protected with tert-butyldimethylsilyl group, and the 2′-OH function was subsequently converted to the corresponding O-triflate derivative for the introduction of the nucleobase moieties. These nucleoside derivatives were transformed to 1,5-anhydro-4-O-(P-(2-cyanoethyl)-P-(N,N-diisopropylamino)phosphinyl)-2-deoxy-6- O-monomethoxytrityl-3-O-(tert-butyldimethylsilyD-D-mannitol with either a 2-(N6-benzoyladenin-9-yl) or a 2-(N2-isobutyrylguanin-9-yl) substituent as the building blocks for oligonucleotide synthesis. The corresponding fully modified oligonucleotides afford considerably less stable duplexes with RNA as compared to the 3-deoxy hexitol nucleic acid analogues described previously. The reason for the lower stability was investigated using molecular modeling. MD simulations of single strand MNA(GCGTAGCG) and MNA(GCGTAGCG) complexed with RNA(CGCAUCGC) in aqueous solution were performed by use of AMBER 4.1 with the particle mesh Ewald (PME) method for the treatment of long-range electrostatic interactions. Frequent hydrogen bonds between the 3′-hydroxyl and the 6′-O of the phosphate backbone of the following base changed the conformation of the single strand as well as the MNA:RNA complex. The MNA:RNA backbone widens up and shows partial unwinding and disruption of base pair hydrogen bonds consistent with their low hybridization potential.
Synthesis of 1,5-anhydro-D-mannitol nucleosides with a purine base moiety
Hossain, Nafizal,Herdewijn, Piet
, p. 1775 - 1779 (2007/10/03)
D-Mannitol nucleosides with a purine base moiety have been conveniently synthesized strating from 1,5-anhydro-4,6-O-benzylidene-D-glucitol. The 3-OH function of 1,5-anhydro-4,6-O-benzylidene-D-glucitol was selectively protected with t-butyldimethylsilyl group and subsequently converted to the corresponding O-triflate derivative for the introduction of the nucleobase moietes. These nucleoside derivatives were transformed to 1,5-Anhydro-6-O- MMTr-2-(N6-benzoyladenin-9-yl)-2-deoxy-3-O-TBDMS-D-mannitol and 1,5-Anhydro- 6-O-MMTr-2-(N2-isobutyrylguanin-9-yl)-2-deoxy-3-O-TBDMS-D-mannitol, useful as the building blocks for oligonucleotide synthesis. Also, the synthesis of the corresponding fully deprotected anhydrohexitol nucleosides were achieved for evaluation of antiviral activity test.
1,5-Anhydro-2-deoxy-D-altritol oligonucleotides as conformationally restricted analogues of RNA
Allart, Brigitte,Van Aerschot, Arthur,Herdewijn, Piet
, p. 1523 - 1526 (2007/10/03)
As part of a project concerning the investigation of new hexitol nucleic acids (HNA), the 1,5-anhydro-2-deoxy-D-altritol nucleoside building blocks with a uracil, cytosine, adenine and guanine base moiety were synthesized. The uracil analogue was used for the automated synthesis of corresponding oligonucleotides. Hybridization capabilities of these altritol nucleic acids (ANA) are illustrated by the Tm values obtained for the (d(h)U)13/(dA)13 duplex.
Synthesis of 1,5-anhydro-2-(N6-cyclopentyladenin-9-yl)-2-deoxy-D- altrohexitol
Verheggen,Van Aerschot,Pillet,Van der Wenden,Ijzerman,Herdewijn
, p. 321 - 324 (2007/10/02)
The N6-cyclopentyladenosine (CPA) analogue (4) was synthesized in 10 steps starting from glucose. The results of the radioligand binding assays are consistent with the thus far published findings that compounds containing a six-membered moiety at N9 exhibit extremely weak affinity for adenosine receptors. Replacement of the ribofuranosyl moiety of CPA (2) by a 2-deoxy-D-altrohexitol moiety is sufficient to completely abolish its agonist activity.
