81246-79-9Relevant articles and documents
Synthesis, Structural, and Conformational Analysis of 4′-C-Alkyl-2′-O-Ethyl-Uridine Modified Nucleosides
Nikam, Rahul R.,Harikrishna,Gore, Kiran R.
, p. 924 - 932 (2021/02/01)
Sugar modifications have attracted much attention due to their potential structural and functional influence on therapeutic nucleic acids. Herein, we report the synthesis of dual modified 4′-C-azidomethyl-2′-O-ethyl-uridine (4′-AzM-2′-OEt?U) and 4′-C-aminomethyl-2′-O-ethyl-uridine (4′-AM-2′-OEt?U) nucleosides using linear multi-step synthesis (16 linear steps). Additionally, we report an alternative route for the synthesis of 2′-O-ethyl-uridine nucleoside which has been achieved in three steps with an overall yield of 40 %. X-ray structure of 4′-AzM-2′-OEt?U illustrates that the nucleoside adopts C2′-endo (South) conformation having a DNA-type glycosidic bond (χ) angle of ?116.01°. Computational studies revealed the C2′-endo and C4′-exo conformations for 4′-AzM-2′-OEt?U and 4′-AM-2′-OEt?U free nucleosides, respectively. The C4′-exo conformation in 4′-AM-2′-OEt?U free nucleoside is collectively stabilized by various non-covalent interactions between positively charged aminomethyl and 2′,3′-hydroxyl groups. Insights into the structural and conformational analysis of dual sugar modified nucleosides and oligonucleotides will be helpful in the rational design of modified nucleosides and therapeutic oligonucleotides.
Azido Functionalized Nucleosides Linked to Controlled Pore Glass as Suitable Starting Materials for Oligonucleotide Synthesis by the Phosphoramidite Approach
Müggenburg, Frederik,Biallas, Alexander,Debiais, Mégane,Smietana, Michael,Müller, Sabine
, p. 6408 - 6416 (2021/11/30)
It has long been debated whether easily reducible azide groups can withstand the conditions of oligonucleotide synthesis by phosphoramidite chemistry. We have synthesized various 2′- and 3′-azido modified nucleosides and immobilized them on controlled pore glass (CPG) to be used as starting material for the synthesis of oligonucleotides (ONs) with 3′-terminal azide (attached to C2′ or C3′). In a model study, immobilized 3′-azidoadenosine was used as a starting block for the synthesis of a series of oligodeoxynucleotides (ODNs) of increasing length. Upon synthesis, the ODNs were enzymatically digested into monomers and analyzed by RP-HPLC. A peak corresponding to 3′-azidoadenosine was clearly identified in all samples. Quantitative analysis showed that 3′-azidoadenosine was present in nearly the expected ratio to deoxycytidine, which was used as an internal standard. Most importantly, the ratio remained the same for all three ODNs regardless of their length, demonstrating that a higher number of coupling cycles does not lead to higher degradation of the azide. Thus, 2′- or 3′-azido nucleosides attached to a solid support are excellent starting materials for the synthesis of oligonucleotides with 3′-terminal azide.
UNA AMIDITES AND USES THEREOF
-
Paragraph 0343; 0347, (2020/12/29)
Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a disease which utilize a composition or
