The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Biliang Zhang - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 5'-deoxy-5'-Thioguanosine-5'-monophosphorothioate and its incorporation into RNA 5'-termini.
Organic Letters, 2001Co-Authors: Biliang ZhangAbstract:5‘-Deoxy-5‘-Thioguanosine-5‘-monophosphorothioate (GSMP) was synthesized in four steps with 35% overall yield. GSMP serves as a good substrate for in vitro transcription with T7 RNA polymerase to yield 5‘-GSMP-RNA, which was converted to 5‘-HS-RNA by dephosphorylation with alkaline phosphatase. The thiol-reactive agents can be efficiently introduced into the 5‘-terminus of RNA.
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Synthesis of 5'-deoxy-5'-Thioguanosine-5'-monophosphorothioate and its incorporation into RNA 5'-termini.
Organic letters, 2001Co-Authors: Biliang Zhang, Zhiyong Cui, Lele SunAbstract:[figure: see text] 5'-Deoxy-5'-Thioguanosine-5'-monophosphorothioate (GSMP) was synthesized in four steps with 35% overall yield. GSMP serves as a good substrate for in vitro transcription with T7 RNA polymerase to yield 5'-GSMP-RNA, which was converted to 5'-HS-RNA by dephosphorylation with alkaline phosphatase. The thiol-reactive agents can be efficiently introduced into the 5'-terminus of RNA.
Ganapathi R. Revankar - One of the best experts on this subject based on the ideXlab platform.
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incorporation of 2 deoxy 9 deazaguanosine and 2 deoxy 7 deaza 6 Thioguanosine into g rich oligodeoxyribonucleotides
Nucleosides Nucleotides & Nucleic Acids, 1995Co-Authors: Sudhakar T Rao, Theresa Schmaltz Hill, Arthur F. Lewis, Ganapathi R. RevankarAbstract:Abstract The preparation of suitably protected monomeric phosphoramidite building blocks of 2′-deoxy-9-deazaguanosine (8) and 2′-deoxy-7-deaza-6-Thioguanosine (12) and their incorporation into G-rich Oligodeoxyribonucleotides are described.
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Incorporation of 2'-deoxy-6-Thioguanosine into G-rich oligodeoxyribonucleotides inhibits G-tetrad formation and facilitates triplex formation.
Biochemistry, 1995Co-Authors: T. Sudhakar Rao, Ross H. Durland, Dale M. Seth, Melissa A. Myrick, Veeraiah Bodepudi, Ganapathi R. RevankarAbstract:An efficient and expeditious method for the synthesis of S6-(cyanoethyl)-N2-isobutyryl (or trifluoroacetyl)-2'-deoxy-6-Thioguanosine (7 and 2) from 2'-deoxyguanosine (G) has been developed. Compound 7 has been incorporated into several G-rich triple-helix-forming oligonucleotides (TFOs) using solid-support, phosphoramidite chemistry. The purified oligonucleotides containing 2'-deoxy-6-Thioguanosine (S6-dG) residues in the place of G have been characterized by nucleoside composition analysis. These modified TFOs have been shown to be stable in aqueous, as well as buffered, solutions normally used to assay triple-helix formation. It has also been demonstrated that partial incorporation of S6-dG is effective in inhibiting the formation of G tetrads in G-rich oligodeoxyribonucleotides, thus facilitating triple-helix formation in potassium-containing buffers.
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Incorporation of 2′-Deoxy-9-deazaguanosine and 2′-Deoxy-7-deaza-6-Thioguanosine into G-Rich Oligodeoxyribonucleotides
Nucleosides and Nucleotides, 1995Co-Authors: T. Sudhakar Rao, Arthur F. Lewis, Theresa Schmaltz Hill, Ganapathi R. RevankarAbstract:Abstract The preparation of suitably protected monomeric phosphoramidite building blocks of 2′-deoxy-9-deazaguanosine (8) and 2′-deoxy-7-deaza-6-Thioguanosine (12) and their incorporation into G-rich Oligodeoxyribonucleotides are described.
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a novel synthesis of s6 cyanoethyl 2 deoxy 6 Thioguanosine and its incorporation into triple helix forming oligonucleotides
Tetrahedron Letters, 1992Co-Authors: Sudhakar T Rao, Ross H. Durland, Krishna Jayaraman, Ganapathi R. RevankarAbstract:Abstract A simple and expeditious synthesis of S 6 -cyanoethyl-2′-deoxy-6-Thioguanosine from 2′-deoxyguanosine has been accomplished in good yield and incorporated into several triple helix forming oligonucleotides using the solid-phase phosphoramidite chemistry.
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A novel synthesis of S6-cyanoethyl-2′-deoxy-6-Thioguanosine and its incorporation into triple helix forming oligonucleotides☆
Tetrahedron Letters, 1992Co-Authors: T. Sudhakar Rao, Ross H. Durland, Krishna Jayaraman, Ganapathi R. RevankarAbstract:Abstract A simple and expeditious synthesis of S 6 -cyanoethyl-2′-deoxy-6-Thioguanosine from 2′-deoxyguanosine has been accomplished in good yield and incorporated into several triple helix forming oligonucleotides using the solid-phase phosphoramidite chemistry.
Lele Sun - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 5'-deoxy-5'-Thioguanosine-5'-monophosphorothioate and its incorporation into RNA 5'-termini.
Organic letters, 2001Co-Authors: Biliang Zhang, Zhiyong Cui, Lele SunAbstract:[figure: see text] 5'-Deoxy-5'-Thioguanosine-5'-monophosphorothioate (GSMP) was synthesized in four steps with 35% overall yield. GSMP serves as a good substrate for in vitro transcription with T7 RNA polymerase to yield 5'-GSMP-RNA, which was converted to 5'-HS-RNA by dephosphorylation with alkaline phosphatase. The thiol-reactive agents can be efficiently introduced into the 5'-terminus of RNA.
Matthias Schwab - One of the best experts on this subject based on the ideXlab platform.
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Determination of 6-Thioguanosine diphosphate and triphosphate and nucleoside diphosphate kinase activity in erythrocytes: novel targets for thiopurine therapy?
Therapeutic drug monitoring, 2010Co-Authors: Susanne Karner, Shaojun Shi, C. Fischer, Elke Schaeffeler, Markus F. Neurath, Klaus Herrlinger, Ute Hofmann, Matthias SchwabAbstract:6-Thioguanine nucleotides are the sum of 6-Thioguanosine 5'-monophosphate (TGMP), -diphosphate (TGDP), and - triphosphate (TGTP) representing essential metabolites involved in drug action of thiopurines. Elevated levels of TGDP have been associated with poor response to azathioprine therapy in patients with inflammatory bowel disease. The conversion of TGDP to TGTP is supposed to be catalyzed by nucleoside diphosphate kinase (NDPK). The aim of this work was to investigate simultaneously individual 6-Thioguanosine phosphate levels and NDPK activity in red blood cells (RBCs) of patients on azathioprine therapy. Ion-pair high-performance liquid chromatography methods with fluorescence and ultraviolet detection were applied to quantify individual levels of 6-Thioguanosine 5'-phosphates and NDPK activity, respectively, in RBCs. Recombinantly expressed NDPK isoforms A and B were unequivocally identified to catalyze the formation of TGTP (30.6 ± 3.88 nmol·min -1 ·mg -1 for NDPK A versus 41.2 ± 1.05 nmol·min -1 ·mg -1 for NDPK B). Comprehensive analyses on the stability of TGMP, TGDP, and TGTP and the reproducibility of NDPK activity in RBCs were performed to provide a reliable sampling protocol for clinical practice. Of note, isolation of RBCs within 6 hours followed by immediate storage at -80°C is crucial for prevention of degradation of 5'-phosphates. In a clinical study of 37 patients on azathioprine, TGTP was the predominant 6-Thioguanosine phosphate in RBCs. In contrast, three patients showed TGTP/ (TGDP + TGTP) ratios of 57.2%, 64.3%, and 66% corresponding to elevated TGDP levels. NDPK activity ranged from 4.1 to 11.3 nmol·min -1 ·mg -1 hemoglobin. No correlation between NDPK activity and the 6-Thioguanosine phosphate levels was found. The question whether interindividual variability of NDPK activity may explain differences in 6-Thioguanosine 5'-phosphates levels has to be investigated in a prospective large-scale study.
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6 Thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in crohn s disease
Clinical Gastroenterology and Hepatology, 2005Co-Authors: Markus F. Neurath, C. Fischer, Ute Hofmann, Ralf Kiesslich, Ute Teichgräber, Michel Eichelbaum, Peter R. Galle, Matthias SchwabAbstract:Background & Aims: Azathioprine is the gold standard for immunosuppressive therapy in Crohn's disease (CD) and its molecular mechanism of action is caused by the metabolite 6-Thioguanosine triphosphate (TGTP). In this study we assessed the impact of TGTP levels for monitoring of azathioprine therapy. Methods: A novel, highly sensitive assay was established to measure levels of TGTP and its precursors 6-Thioguanosine monophosphates and 6-Thioguanosine diphosphates (TGDP) in red blood cells from 50 CD patients. The results were correlated with clinical outcome. Results: TGTP levels could be quantified in 47 patients and a subgroup of these patients showed significantly high levels of TGDP. 6-thioguanine nucleotide (6-TGN) levels showed a significant correlation with TGDP plus TGTP concentrations, suggesting that active TGTP and its inactive precursor TGDP are the main metabolites within 6-TGN. Patients with 6-TGN levels higher than 100 pmol/8 × 10 8 red blood cells showed better response rates, on average, than patients with lower 6-TGN levels. The subgroup of patients with higher 6-TGN and increased TGDP levels showed a worse outcome with lower response rates, more flares, and higher infliximab demand than patients with high 6-TGN, low TGDP, and predominantly detectable TGTP levels. Conclusions: This study shows that quantification of TGTP levels can be used to monitor azathioprine therapy in inflammatory bowel disease patients. Furthermore, the data suggest that TGDP levels of more than 15% of total 6-TGN levels may be a useful surrogate parameter to predict poor response in a subgroup of azathioprine-treated patients.
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6-Thioguanosine Diphosphate and Triphosphate Levels in Red Blood Cells and Response to Azathioprine Therapy in Crohn’s Disease
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2005Co-Authors: Markus F. Neurath, C. Fischer, Ute Hofmann, Ralf Kiesslich, Ute Teichgräber, Michel Eichelbaum, Peter R. Galle, Matthias SchwabAbstract:Background & Aims: Azathioprine is the gold standard for immunosuppressive therapy in Crohn's disease (CD) and its molecular mechanism of action is caused by the metabolite 6-Thioguanosine triphosphate (TGTP). In this study we assessed the impact of TGTP levels for monitoring of azathioprine therapy. Methods: A novel, highly sensitive assay was established to measure levels of TGTP and its precursors 6-Thioguanosine monophosphates and 6-Thioguanosine diphosphates (TGDP) in red blood cells from 50 CD patients. The results were correlated with clinical outcome. Results: TGTP levels could be quantified in 47 patients and a subgroup of these patients showed significantly high levels of TGDP. 6-thioguanine nucleotide (6-TGN) levels showed a significant correlation with TGDP plus TGTP concentrations, suggesting that active TGTP and its inactive precursor TGDP are the main metabolites within 6-TGN. Patients with 6-TGN levels higher than 100 pmol/8 × 10 8 red blood cells showed better response rates, on average, than patients with lower 6-TGN levels. The subgroup of patients with higher 6-TGN and increased TGDP levels showed a worse outcome with lower response rates, more flares, and higher infliximab demand than patients with high 6-TGN, low TGDP, and predominantly detectable TGTP levels. Conclusions: This study shows that quantification of TGTP levels can be used to monitor azathioprine therapy in inflammatory bowel disease patients. Furthermore, the data suggest that TGDP levels of more than 15% of total 6-TGN levels may be a useful surrogate parameter to predict poor response in a subgroup of azathioprine-treated patients.
Shigeki Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Development of new 1,3-diazaphenoxazine derivatives (thioG-grasp) to covalently capture 8-Thioguanosine.
Molecules (Basel Switzerland), 2015Co-Authors: Yasufumi Fuchi, Hideto Obayashi, Shigeki SasakiAbstract:The derivatives of 8-Thioguanosine are thought to be included in the signal transduction system related to 8-nitroguanosine. In this study, we attempted to develop new 1,3-diazaphenoxazine (G-clamp) derivatives to covalently capture 8-Thioguanosine (thioG-grasp). It was expected that the chlorine atom at the end of the linker would be displaced by the nucleophilic attack by the sulfur atom of 8-Thioguanosine via multiple hydrogen-bonded complexes. The thioG-grasp derivative with a propyl linker reacted efficiently with 8-Thioguanosine to form the corresponding adduct.
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An efficient and simple method for site-selective modification of O6-methyl-2'-deoxyguanosine in DNA.
Chemical communications (Cambridge England), 2012Co-Authors: Kazumitsu Onizuka, Yosuke Taniguchi, Takamasa Nishioka, Daichi Jitsuzaki, Shigeki SasakiAbstract:O 6-Methyl-2′-deoxyguanosine (O6-Me-dG) is a mutagenic nucleotide in DNA. O6-Me-dG in DNA was rapidly and selectively modified by a functionality transfer reaction using the ODN incorporating 6-S-functionalized Thioguanosine. Subsequent labelling of O6-Me-dG with the fluorescent FAM or biotin group via click chemistry has permitted the sensitive and selective detection of O6-Me-dG in DNA.
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oligodeoxynucleotide containing s functionalized 2 deoxy 6 Thioguanosine facile tools for base selective and site specific internal modification of rna
Current protocols in human genetics, 2012Co-Authors: Shigeki Sasaki, Kazumitsu Onizuka, Yosuke TaniguchiAbstract:Chemically modified oligonucleotides play a significant role for genomic research. Modified nucleosides, such as with a fluorescent dye, can be obtained by chemical synthesis. Site-specifically modified long nucleic acids are obtained by ligation of chemically modified short oligonucleotides with enzyme, photochemistry, or catalytic DNA. The functionality-transfer ODN (FT-ODN), which contains 2′-deoxy-6-Thioguanosine (6-thio-dG) functionalized with the 2-methyliden-1,3-diketone group, is hybridized with the target RNA to trigger the selective functionalization of the 4-amino group of the cytosine base at pH 7 or the 2-amino group of the guanine base at pH 9.4 or at pH 7.4 in the presence of NiCl2. In particular, the functionality-transfer reaction (FTR) under the alkaline conditions or neutral conditions in the presence of NiCl2 proceeds rapidly and selectively to lead to the modification of the target guanine. The transfer reaction of the acetylene-containing diketone group produces the acetylene-modified RNA, which can be subjected to the Cu(I)-catalyzed “click chemistry” with a variety of azide compounds for highly specific, internal modification of RNA. Curr. Protoc. Nucleic Acid Chem. 48:4.49.1-4.49.16. © 2012 by John Wiley & Sons, Inc. Keywords: 2′-deoxy-6-Thioguanosine; RNA modification; functionality transfer; click chemistry
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Current Protocols in Nucleic Acid Chemistry - Oligodeoxynucleotide containing s-functionalized 2'-deoxy-6-Thioguanosine: facile tools for base-selective and site-specific internal modification of RNA.
Current Protocols in Nucleic Acid Chemistry, 2012Co-Authors: Shigeki Sasaki, Kazumitsu Onizuka, Yosuke TaniguchiAbstract:Chemically modified oligonucleotides play a significant role for genomic research. Modified nucleosides, such as with a fluorescent dye, can be obtained by chemical synthesis. Site-specifically modified long nucleic acids are obtained by ligation of chemically modified short oligonucleotides with enzyme, photochemistry, or catalytic DNA. The functionality-transfer ODN (FT-ODN), which contains 2′-deoxy-6-Thioguanosine (6-thio-dG) functionalized with the 2-methyliden-1,3-diketone group, is hybridized with the target RNA to trigger the selective functionalization of the 4-amino group of the cytosine base at pH 7 or the 2-amino group of the guanine base at pH 9.4 or at pH 7.4 in the presence of NiCl2. In particular, the functionality-transfer reaction (FTR) under the alkaline conditions or neutral conditions in the presence of NiCl2 proceeds rapidly and selectively to lead to the modification of the target guanine. The transfer reaction of the acetylene-containing diketone group produces the acetylene-modified RNA, which can be subjected to the Cu(I)-catalyzed “click chemistry” with a variety of azide compounds for highly specific, internal modification of RNA. Curr. Protoc. Nucleic Acid Chem. 48:4.49.1-4.49.16. © 2012 by John Wiley & Sons, Inc. Keywords: 2′-deoxy-6-Thioguanosine; RNA modification; functionality transfer; click chemistry
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Activation and alteration of base selectivity by metal cations in the functionality-transfer reaction for RNA modification.
Bioconjugate chemistry, 2010Co-Authors: Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki SasakiAbstract:Previously, we reported that the 2-methylidene-1,3-diketone unit of 6-Thioguanosine transferred selectively to the amino group of cytosine at pH 7.0 and that its selectivity was changed to the guanine base at pH 9.6. In this study, it was found that the functionality-transfer reaction enhanced selectivity for the guanine base in the presence of divalent transition metal cations such as Ni2+ and Co2+ at pH 7.4.
