- Synthesis and conformational analysis of 1′- and 3′-substituted 2-deoxy-2-fluoro-D-ribofuranosyl nucleosides
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Convergent syntheses of the 9-(3-X-2,3-dideoxy-2-fluoro-β-D- ribofuranosyl)adenines 5 (X = N3) and 7 (X = NH2), as well as of their respective α-anomers 6 and 8, are described, using methyl 2-azido-5-O-benzoyl-2,3-dideoxy-2-fluoro-β-D-ribofuranoside (4) as glycosylating agent. Methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-β-D- ribofuranoside (12) was prepared starting from two precursors, and coupled with silylated N6-benzoyladenine to afford, after deprotection, 2′,3′-dideoxy-2′,3′-difluoroadenosine (13). Condensation of 1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-ribofuranose (14) with silylated N2-palmitoylguanine gave, after chromatographic separation and deacylation, the N7-β-anomer 17 as the main product, along with 2′-deoxy-2′-fluoroguanosine (15) and its N9-α- anomer 16 in a ratio of ca. 42:24:10. An in-depth conformational analysis of a number of 2,3-dideoxy-2-fluoro-3-X-D-ribofuranosides (X = F, N3, NH2, H) as well as of purine and pyrimidine 2-deoxy-2-fluoro-D- ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.
- Sivets, Grigorii G.,Kalinichenko, Elena N.,Mikhailopulo, Igor A.
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p. 1818 - 1836
(2008/03/12)
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- Antisense modulation of CD40 ligand expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.
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Page/Page column 17-18
(2008/06/13)
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- Modulation of DC-SIGN expression
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Compounds, compositions and methods are provided for modulating the expression of DC-SIGN. The compositions comprise oligonucleotides, targeted to nucleic acid encoding DC-SIGN. Methods of using these compounds for modulation of DC-SIGN expression and for diagnosis and treatment of diseases and conditions associated with expression of DC-SIGN are provided.
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Page/Page column 12
(2008/06/13)
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- Modulation of CEACAM1 expression
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Compounds, compositions and methods are provided for modulating the expression of CEACAM1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding CEACAM1. Methods of using these compounds for modulation of CEACAM1 expression and for diagnosis and treatment of disease associated with expression of CEACAM1 are provided.
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Page/Page column 26
(2010/02/11)
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- Antisense modulation of polo-like kinase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of polo-like kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding polo-like kinase. Methods of using these compounds for modulation of polo-like kinase expression and for treatment of diseases associated with expression of polo-like kinase are provided.
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Page/Page column 18
(2008/06/13)
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- ANTISENSE MODULATION OF ENDOTHELIAL LIPASE EXPRESSION
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Antisense compounds, compositions and methods are provided for modulating the expression of Endothelial Lipase (EL). The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EL. Methods of using these compounds for modulation of EL expression and for treatment of diseases associated with expression of EL are provided.
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- Antisense modulation of PPP3CB expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PPP3CB. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PPP3CB. Methods of using these compounds for modulation of PPP3CB expression and for treatment of diseases associated with expression of PPP3CB are provided.
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Page/Page column 18
(2008/06/13)
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- Modulation of diacylglycerol acyltransferase 1 expression
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Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1 are provided.
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Page/Page column 12
(2008/06/13)
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- Antisense modulation of Notch (Drosophila) homolog 4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Notch (Drosophila) homolog 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Notch (Drosophila) homolog 4. Methods of using these compounds for modulation of Notch (Drosophila) homolog 4 expression and for treatment of diseases associated with expression of Notch (Drosophila) homolog 4 are provided.
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Page/Page column 16
(2010/02/06)
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- Antisense modulation of G protein-coupled receptor 12 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor 12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G protein-coupled receptor 12. Methods of using these compounds for modulation of G protein-coupled receptor 12 expression and for treatment of diseases associated with expression of G protein-coupled receptor 12 are provided.
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Page/Page column 19
(2010/11/30)
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- Antisense modulation of perilipin expression
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Antisense compounds, compositions and methods are provided for modulating the expression of perilipin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding perilipin. Methods of using these compounds for modulation of perilipin expression and for treatment of diseases associated with expression of perilipin are provided.
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Page/Page column 18
(2008/06/13)
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- Antisense modulation of EDG5 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of EDG5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EDG5. Methods of using these compounds for modulation of EDG5 expression and for treatment of diseases associated with expression of EDG5 are provided.
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Page/Page column 18
(2008/06/13)
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- ANTISENSE MODULATION OF EDG1 EXPRESSION
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Antisense compounds, compositions and methods are provided for modulating the expression of EDG1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EDG1. Methods of using these compounds for modulation of EDG1 expression and for treatment of diseases associated with expression of EDG1 are provided.
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Page/Page column 18
(2008/06/13)
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- Antisense modulation of MARK3 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of MARK3. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MARK3. Methods of using these compounds for modulation of MARK3 expression and for treatment of diseases associated with expression of MARK3 are provided.
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- Antisense modulation of histone deacetylase 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of histone deacetylase 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding histone deacetylase 2. Methods of using these compounds for modulation of histone deacetylase 2 expression and for treatment of diseases associated with expression of histone deacetylase 2 are provided.
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- Antisense modulation of G protein-coupled receptor kinase 6 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor kinase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G protein-coupled receptor kinase 6. Methods of using these compounds for modulation of G protein-coupled receptor kinase 6 expression and for treatment of diseases associated with expression of G protein-coupled receptor kinase 6 are provided.
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- Antisense modulation of prox-1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of prox-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding prox-1. Methods of using these compounds for modulation of prox-1 expression and for treatment of diseases associated with expression of prox-1 are provided.
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-
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- Antisense modulation of PPP3R1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PPP3R1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PPP3R1. Methods of using these compounds for modulation of PPP3R1 expression and for treatment of diseases associated with expression of PPP3R1 are provided.
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- Antisense modulation of phosphoinositide-3-kinase, regulatory subunit 4, p150 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of phosphoinositide-3-kinase, regulatory subunit 4, p150. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding phosphoinositide-3-kinase, regulatory subunit 4, p150. Methods of using these compounds for modulation of phosphoinositide-3-kinase, regulatory subunit 4, p150 expression and for treatment of diseases associated with expression of phosphoinositide-3-kinase, regulatory subunit 4, p150 are provided.
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- Antisense modulation of Rb2/p130 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Rb2/p130. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Rb2/p130. Methods of using these compounds for modulation of Rb2/p130 expression and for treatment of diseases associated with expression of Rb2/p130 are provided.
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- Notch1 inhibitors for inducing apoptosis
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Compounds, compositions and methods are provided for modulating the expression of Notch1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding Notch1. Methods of using these compounds for modulation of Notch1 expression and for diagnosis and treatment of disease associated with expression Notch1 are provided.
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- Antisense modulation of PLML expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PLML. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PLML. Methods of using these compounds for modulation of PLML expression and for treatment of diseases associated with expression of PLML are provided.
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- Chemical and enzymatic synthesis and antiviral properties of 2'-deoxy- 2'-fluoroguanosine
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Chemical and enzymatic methods were employed for the synthesis of the title compound, 2'F-Guo 7. High antiviral activity of 2'F-Guo was established in chick embryo cells infected with influenza virus FPV/Rostock/34 (H7N1) and herpes simplex virus (HSV) type I (1C strain).
- Zaitseva, Galina V.,Zinchenko, Anatoli I.,Barai, Vladimir N.,Pavlova,Boreko, Evgeny I.,Mikhailopulo, Igor A.
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p. 687 - 688
(2007/10/03)
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- An efficient and scalable synthesis of arabinosylguanine and 2′-deoxy-2′-fluoro-guanosine
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An efficient conversion from commercially available 2,6-diaminopurine-2′,3′,5′-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2′-deoxy-2′-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product. Copyright
- Ross, Bruce S.,Springer, Robert H.,Sprankle, Kelly G.,Vasquez, Guillermo
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p. 1645 - 1647
(2007/10/03)
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- Synthesis and biologic activity of purine 2'-deoxy-2'-fluoro- ribonucleosides
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The synthesis of 3,5-di-O-benzoyl-2-deoxy-2-fluoro-D-ribofuranosyl bromide (8) and its reaction with 2,6-dichloropurine by fusion and with mercuric cyanide catalysis is described. The resulting 2,6-dichloro-9-(3,5-di-O- benzoyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)purine (13) was converted to the 2-fluoroadenine (16), the 2-chloroadenine (17), 2,6-diaminopurine (12), and guanine (14) nucleosides by standard procedures. These nucleosides were cytotoxic to a number of cell lines in culture. The 2-haloadenine nucleosides 16 and 17 gave modest increases in lifespan when tested against the P388 leukemia in mice.
- Thomas,Tiwari,Clayton,Secrist III,Montgomery
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p. 309 - 323
(2007/10/02)
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- Uniformly modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets
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'Uniformly' modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and - cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro- modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into 'chimeric' oligonucleotides has been shown to activate mammalian RNase H. 'Uniformly' modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases.
- Kawasaki,Casper,Freier,Lesnik,Zounes,Cummins,Gonzalez,Cook
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p. 831 - 841
(2007/10/02)
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- Studies on Nucleosides and Nucleotides. LXXXVII. Purine Cyclonucleosides. XLII. Synthesis of 2'-Deoxy-2'-fluoroguanosine
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2'-Deoxy-2'-fluoroguanosine (VII) was synthesized starting from 8,2'-anhydro-8-oxy-9-β-D-arabinofuranosylguanine (8,2'-O-cycloguanosine) (I).Compound I was protected at 2-NH2 with an isobutyryl group and at 3'- and 5'-OH with tetrahydrofuranyl groups.The protected compound III was derivatized to the arabino nucleoside V and thence converted to VII by treatment with trifluoromethanesulfonyl chloride and tetra-n-butylammonium fluoride.The resulting 2'-deoxy-2'-fluoroguanosine showed a 3'-endo favored conformation.Keywords - 8,2'-O-cycloguanosine; tetrahydrofuranyl protection; inversion of arabino- to 2'-fluoro-2'-deoxyribofuranose; NMR; UV; PPC; TLC
- Ikehara, Morio,Imura, Junko
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p. 1034 - 1038
(2007/10/02)
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