- S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS
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Various embodiments provide STOPS? polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS? modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS? modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.
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- Probing Synergistic Effects of DNA Methylation and 2′-β-Fluorination on i-Motif Stability
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The possible role of DNA i-motif structures in telomere biology and in the transcriptional regulation of oncogene promoter regions is supported by several recent studies. Herein we investigate the effect of four cytidine nucleosides (and combinations thereof) on i-motif structure and stability, namely 2′-deoxycytidine (dC), 2′-deoxy-5-methyl-cytidine (5-Me-dC), 2′-deoxy-2′-fluoro-arabinocytidine (2′F-araC), and 2′-deoxy-2′-fluoro-5-methyl-arabinocytidine (5-Me-2′F-araC). The base pair 5-Me-2′F-araC:2′F-araC produced i-motifs with a pH1/2 (“pKa”) value that closely matches physiological pH (7.34±0.3). NMR analysis of the most stable telomeric sequence (HJ-2) at pH 7.0 indicated that the structure is stabilized by hybrid 5-Me-dC:2′F-araC hemiprotonated base pairs and therefore highlights the significance of the interplay between base and sugar modifications on the stability of i-motif structures.
- Abou Assi, Hala,Lin, Yu Chen,Serrano, Israel,González, Carlos,Damha, Masad J.
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p. 471 - 477
(2017/12/15)
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- Synthesis and anti-HIV activity of 2′-deoxy-2′-fluoro-4′-C-ethynyl nucleoside analogs
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Based on the favorable antiviral profiles of 4′-substituted nucleosides, novel 1-(2′-deoxy-2′-fluoro-4′-C-ethynyl-β-d-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC50 values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug.
- Wang, Qiang,Li, Yanfeng,Song, Chuanjun,Qian, Keduo,Chen, Chin-Ho,Lee, Kuo-Hsiung,Chang, Junbiao
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supporting information; experimental part
p. 4053 - 4056
(2010/08/19)
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- Synthesis of 2′-deoxy-2′-fluoro-1-β-D-arabinofuranosyl uracil derivatives: A method suitable for preparation of [18F]-labeled nucleosides
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N-glycosylation of 2,4-bis-O-(trimethylsilyl)-pyrimidine bases with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-l-(Br, OBz)-α-D-arabinose derivatives are reported. 1-Bromo-arabinose provides high yield and a favorable anomeric ratio (β/α) of pyrimidine nucleoside i
- Alauddin, Mian M.,Conti, Peter S.,Fissekis, John D.,Watanabe, Kyoihci A.
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p. 1757 - 1764
(2007/10/03)
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- Antiviral Nucleosides. A Stereospecific, Total Synthesis of 2'-Fluoro-2'-deoxy-β-D-arabinofuranosyl Nucleosides
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A general, total synthesis of (2'-fluoro-2'-deoxy-β-D-arabinofuranosyl)uracils 1a-d is described.A study of the coupling reaction beetwen 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl bromide (7) and silylated pyrimidines 11a-d has resulted in a high overall yield for the five-step stereospecific synthesis of β-nucleosides.
- Howell, Henry G.,Brodfuehrer, Paul R.,Brundidge, Steven P.,Benigni, Daniel A.,Sapino, Chester
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