689221-47-4Relevant articles and documents
β-Methyl-2-amino-2,3-didesoxyribofuranoside, a Novel Building Block for Backbone Modified Antisense Oligonucleotides
Winkler, Johannes,Urban, Ernst,Noe, Christian R.
, p. 109 - 116 (2007/10/03)
A synthesis of the amino sugar 2-amino-2,3-didesoxyribose is described. Starting from D-glucosamine, β-methylfuranoside was obtained in eight steps in 20% yield. This carbohydrate is a novel building block for nucleosides and for backbone modified antisense oligonucleotides with 2′-5′ amide linkages.
Structural modifications of antisense oligonucleotides
Urban, Ernst,Noe, Christian R.
, p. 243 - 258 (2007/10/03)
Antisense oligonucleotides are efficient tools for the inhibition of gene expression in a sequence specific way. Natural oligonucleotides are decomposed rapidly in biological systems, which strongly restrict their application. In contrast, artificial oligonucleotides are designed to be more stable against degradation than the target mRNA, which results in a catalytic effect of the drug. Modification of the phosphate linkage has been the first successful strategy for antisense drug developments and Fomivirsene the first antisense drug in therapy. The launch of Fomivirsene has resulted in a revolutionary spin off to antisense research leading to a second generation of antisense oligonucleotides, which are stable against oligonucleotide cleaving enzymes. Among these, oligonucleotides bearing an alkoxy substituent in position 2′ were the most successful ones. The third generation of antisense oligonucleotides contains structure elements, which enhance the antisense action. Zwitterionic oligonucleotides show remarkable results, first, because the stability against ribozymes is largely increased, and secondly, because the electrostatic repulsion between the anionic sense and the zwitterionic antisense cords is minimized. Promising new target molecules in antisense reseach are oligonucleotide chimaeres, which enhance the antisense action (chimaeres with intercalators, chelators or polyamines) or enable an application as sequence specific detectors (chimaeres with biotin, fluorescein or radioligands).
