171268-85-2Relevant academic research and scientific papers
Regulating angiogenesis with light-inducible antimirs
Schaefer, Florian,Wagner, Jasmin,Knau, Andrea,Dimmeler, Stefanie,Heckel, Alexander
, p. 13558 - 13561 (2013)
The inhibition of microRNAs (miRs) in a spatiotemporally defined manner by an exogenous trigger would help to specifically target the biological activity and avoid off-target effects. Novel antimiRs directed against miR-92a can be activated by irradiation (see scheme; 3′-UTR=3′-untranslated region) In this way miR-92a is inhibited, the miR-92a target integrin α5 is derepressed, and angiogenesis of endothelial cells is enhanced. Copyright
Facile Synthesis, Geometry, and 2′-Substituent-Dependent in Vivo Activity of 5′-(E)- and 5′-(Z)-Vinylphosphonate-Modified siRNA Conjugates
Parmar, Rubina Giare,Brown, Christopher R.,Matsuda, Shigeo,Willoughby, Jennifer L. S.,Theile, Christopher S.,Charissé, Klaus,Foster, Donald J.,Zlatev, Ivan,Jadhav, Vasant,Maier, Martin A.,Egli, Martin,Manoharan, Muthiah,Rajeev, Kallanthottathil G.
, p. 734 - 744 (2018/02/17)
(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5′-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5′-end of oligonucleotides under standard solid-phase synthesis and deprotection conditions by utilizing pivaloyloxymethyl (POM) protected VP-nucleoside phosphoramidites. The POM protection enhances scope and scalability of 5′-VP-modified oligonucleotides and, in a broader sense, the synthesis of oligonucleotides modified with phosphonate moieties. Trivalent N-acetylgalactosamine-conjugated small interfering RNA (GalNAc-siRNA) comprising (E)-geometrical isomer of VP showed improved RISC loading with robust RNAi-mediated gene silencing in mice compared to the corresponding (Z)-isomer despite similar tissue accumulation. We also obtained structural insights into why bulkier 2′-ribosugar substitutions such as 2′-O-[2-(methylamino)-2-oxoethyl] are well tolerated only when combined with 5′-(E)-VP.
Synthesis and anti-HCV activity of 3′,4′-oxetane nucleosides
Chang, Wonsuk,Du, Jinfa,Rachakonda, Suguna,Ross, Bruce S.,Convers-Reignier, Serge,Yau, Wei T.,Pons, Jean-Francois,Murakami, Eisuke,Bao, Haiying,Steuer, Holly Micolochick,Furman, Phillip A.,Otto, Michael J.,Sofia, Michael J.
scheme or table, p. 4539 - 4543 (2010/11/03)
Hepatitis C virus afflicts approximately 180 million people worldwide and currently there are no direct acting antiviral agents available to treat this disease. Our first generation nucleoside HCV inhibitor, RG7128 has already established proof-of-concept
