The Experts below are selected from a list of 3801 Experts worldwide ranked by ideXlab platform
Hidetaka Torigoe - One of the best experts on this subject based on the ideXlab platform.
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2'-O,4'-C-ethylene bridged Nucleic Acid Modification enhances pyrimidine motif triplex-forming ability under physiological condition.
Journal of Biochemistry, 2012Co-Authors: Hidetaka Torigoe, Norihiro Sato, Nobuyuki NagasawaAbstract:Since pyrimidine motif triplex DNA is unstable at physiological neutral pH, triplex stabilization at physiological neutral pH is important for improvement of its potential to be applied to various methods in vivo, such as repression of gene expression, mapping of genomic DNA and gene-targeted mutagenesis. For this purpose, we studied the thermodynamic and kinetic effects of a chemical Modification, 2'-O,4'-C-ethylene bridged Nucleic Acid (ENA) Modification of triplex-forming oligonucleotide (TFO), on pyrimidine motif triplex formation at physiological neutral pH. Thermodynamic investigations indicated that the Modification achieved more than 10-fold increase in the binding constant of the triplex formation. The increased number of the Modification in TFO enhanced the increased magnitude of the binding constant. On the basis of the obtained thermodynamic parameters, we suggested that the remarkably increased binding constant by the Modification may result from the increased stiffness of TFO in the unbound state. Kinetic studies showed that the considerably decreased dissociation rate constant resulted in the observed increased binding constant by the Modification. We conclude that ENA Modification of TFO could be a useful chemical Modification to promote the triplex formation under physiological neutral condition, and may advance various triplex formation-based methods in vivo.
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2'-O,4'-C-aminomethylene-bridged Nucleic Acid Modification with enhancement of nuclease resistance promotes pyrimidine motif triplex Nucleic Acid formation at physiological pH.
Chemistry - A European Journal, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to the instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex-formation-based strategies in vivo, such as gene expression regulation, genomic DNA mapping, and gene-targeted mutagenesis. To this end, we investigated the thermodynamic and kinetic effects of our previously reported chemical Modification, 2'-O,4'-C-aminomethylene-bridged Nucleic Acid (2',4'-BNA(NC)) Modification of triplex-forming oligonucleotide (TFO), on triplex formation at physiological pH. The thermodynamic analyses indicated that the 2',4'-BNA(NC) Modification of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold. The number and position of the 2',4'-BNA(NC) Modification in TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity and the increased degree of hydration of the 2',4'-BNA(NC)-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant. Kinetic data demonstrated that the observed increase in the binding constant by the 2',4'-BNA(NC) Modification resulted mainly from the considerable decrease in the dissociation rate constant. The TFO stability in human serum showed that the 2',4'-BNA(NC) Modification significantly increased the nuclease resistance of TFO. Our results support the idea that the 2',4'-BNA(NC) Modification of TFO could be a key chemical Modification to achieve higher binding affinity and higher nuclease resistance in the triplex formation under physiological conditions, and may lead to progress in various triplex-formation-based strategies in vivo.
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interrupted 2 o 4 c aminomethylene bridged Nucleic Acid Modification enhances pyrimidine motif triplex forming ability and nuclease resistance under physiological condition
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, S Abdur M Rahman, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition
Nucleosides Nucleotides and Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Promotion of triplex formation by 3′-amino-2′-O,4′-C-methylene bridged Nucleic Acid Modification
Nucleic Acids Symposium Series, 2009Co-Authors: Kiyomi Sasaki, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hidetaka TorigoeAbstract:We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid (3'-amino-2',4'-BNA) backbone Modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA Modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA Modification of TFO could be a key chemical Modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
Takeshi Imanishi - One of the best experts on this subject based on the ideXlab platform.
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2'-O,4'-C-aminomethylene-bridged Nucleic Acid Modification with enhancement of nuclease resistance promotes pyrimidine motif triplex Nucleic Acid formation at physiological pH.
Chemistry - A European Journal, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to the instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex-formation-based strategies in vivo, such as gene expression regulation, genomic DNA mapping, and gene-targeted mutagenesis. To this end, we investigated the thermodynamic and kinetic effects of our previously reported chemical Modification, 2'-O,4'-C-aminomethylene-bridged Nucleic Acid (2',4'-BNA(NC)) Modification of triplex-forming oligonucleotide (TFO), on triplex formation at physiological pH. The thermodynamic analyses indicated that the 2',4'-BNA(NC) Modification of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold. The number and position of the 2',4'-BNA(NC) Modification in TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity and the increased degree of hydration of the 2',4'-BNA(NC)-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant. Kinetic data demonstrated that the observed increase in the binding constant by the 2',4'-BNA(NC) Modification resulted mainly from the considerable decrease in the dissociation rate constant. The TFO stability in human serum showed that the 2',4'-BNA(NC) Modification significantly increased the nuclease resistance of TFO. Our results support the idea that the 2',4'-BNA(NC) Modification of TFO could be a key chemical Modification to achieve higher binding affinity and higher nuclease resistance in the triplex formation under physiological conditions, and may lead to progress in various triplex-formation-based strategies in vivo.
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interrupted 2 o 4 c aminomethylene bridged Nucleic Acid Modification enhances pyrimidine motif triplex forming ability and nuclease resistance under physiological condition
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, S Abdur M Rahman, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition
Nucleosides Nucleotides and Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Promotion of triplex formation by 3′-amino-2′-O,4′-C-methylene bridged Nucleic Acid Modification
Nucleic Acids Symposium Series, 2009Co-Authors: Kiyomi Sasaki, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hidetaka TorigoeAbstract:We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid (3'-amino-2',4'-BNA) backbone Modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA Modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA Modification of TFO could be a key chemical Modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
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Synergistic Stabilization of Nucleic Acid Assembly by 2′-O,4′-C-Methylene-Bridged Nucleic Acid Modification and Additions of Comb-Type Cationic Copolymers†
Biochemistry, 2009Co-Authors: Hidetaka Torigoe, Satoshi Obika, Takeshi Imanishi, Atushi Maruyama, Takuma KatayamaAbstract:Stabilization of Nucleic Acid assemblies, such as duplex and triplex, is quite important for their wide variety of potential applications. Various stabilization methods, including molecular designs of chemically modified nucleotides and hybrid stabilizers, and combinations of different stabilization methods have been developed to increase stability of Nucleic Acid assemblies. However, combinations of two stabilizing methods have not always yielded desired synergistic effects. In the present study, to propose a strategy for selection of a rational combination of stabilizing methods, we demonstrate synergistic stabilization of triplex by 2′-O,4′-C-methylene-bridged Nucleic Acid (2′,4′-BNA) Modification of triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of these methods increased the binding constant for triplex formation by nearly 2 orders of magnitude. However, their kinetic contributions were quite d...
Satoshi Obika - One of the best experts on this subject based on the ideXlab platform.
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2'-O,4'-C-aminomethylene-bridged Nucleic Acid Modification with enhancement of nuclease resistance promotes pyrimidine motif triplex Nucleic Acid formation at physiological pH.
Chemistry - A European Journal, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to the instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex-formation-based strategies in vivo, such as gene expression regulation, genomic DNA mapping, and gene-targeted mutagenesis. To this end, we investigated the thermodynamic and kinetic effects of our previously reported chemical Modification, 2'-O,4'-C-aminomethylene-bridged Nucleic Acid (2',4'-BNA(NC)) Modification of triplex-forming oligonucleotide (TFO), on triplex formation at physiological pH. The thermodynamic analyses indicated that the 2',4'-BNA(NC) Modification of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold. The number and position of the 2',4'-BNA(NC) Modification in TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity and the increased degree of hydration of the 2',4'-BNA(NC)-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant. Kinetic data demonstrated that the observed increase in the binding constant by the 2',4'-BNA(NC) Modification resulted mainly from the considerable decrease in the dissociation rate constant. The TFO stability in human serum showed that the 2',4'-BNA(NC) Modification significantly increased the nuclease resistance of TFO. Our results support the idea that the 2',4'-BNA(NC) Modification of TFO could be a key chemical Modification to achieve higher binding affinity and higher nuclease resistance in the triplex formation under physiological conditions, and may lead to progress in various triplex-formation-based strategies in vivo.
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interrupted 2 o 4 c aminomethylene bridged Nucleic Acid Modification enhances pyrimidine motif triplex forming ability and nuclease resistance under physiological condition
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, S Abdur M Rahman, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition
Nucleosides Nucleotides and Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Promotion of triplex formation by 3′-amino-2′-O,4′-C-methylene bridged Nucleic Acid Modification
Nucleic Acids Symposium Series, 2009Co-Authors: Kiyomi Sasaki, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hidetaka TorigoeAbstract:We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid (3'-amino-2',4'-BNA) backbone Modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA Modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA Modification of TFO could be a key chemical Modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
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Synergistic Stabilization of Nucleic Acid Assembly by 2′-O,4′-C-Methylene-Bridged Nucleic Acid Modification and Additions of Comb-Type Cationic Copolymers†
Biochemistry, 2009Co-Authors: Hidetaka Torigoe, Satoshi Obika, Takeshi Imanishi, Atushi Maruyama, Takuma KatayamaAbstract:Stabilization of Nucleic Acid assemblies, such as duplex and triplex, is quite important for their wide variety of potential applications. Various stabilization methods, including molecular designs of chemically modified nucleotides and hybrid stabilizers, and combinations of different stabilization methods have been developed to increase stability of Nucleic Acid assemblies. However, combinations of two stabilizing methods have not always yielded desired synergistic effects. In the present study, to propose a strategy for selection of a rational combination of stabilizing methods, we demonstrate synergistic stabilization of triplex by 2′-O,4′-C-methylene-bridged Nucleic Acid (2′,4′-BNA) Modification of triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of these methods increased the binding constant for triplex formation by nearly 2 orders of magnitude. However, their kinetic contributions were quite d...
Kiyomi Sasaki - One of the best experts on this subject based on the ideXlab platform.
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2'-O,4'-C-aminomethylene-bridged Nucleic Acid Modification with enhancement of nuclease resistance promotes pyrimidine motif triplex Nucleic Acid formation at physiological pH.
Chemistry - A European Journal, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to the instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex-formation-based strategies in vivo, such as gene expression regulation, genomic DNA mapping, and gene-targeted mutagenesis. To this end, we investigated the thermodynamic and kinetic effects of our previously reported chemical Modification, 2'-O,4'-C-aminomethylene-bridged Nucleic Acid (2',4'-BNA(NC)) Modification of triplex-forming oligonucleotide (TFO), on triplex formation at physiological pH. The thermodynamic analyses indicated that the 2',4'-BNA(NC) Modification of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold. The number and position of the 2',4'-BNA(NC) Modification in TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity and the increased degree of hydration of the 2',4'-BNA(NC)-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant. Kinetic data demonstrated that the observed increase in the binding constant by the 2',4'-BNA(NC) Modification resulted mainly from the considerable decrease in the dissociation rate constant. The TFO stability in human serum showed that the 2',4'-BNA(NC) Modification significantly increased the nuclease resistance of TFO. Our results support the idea that the 2',4'-BNA(NC) Modification of TFO could be a key chemical Modification to achieve higher binding affinity and higher nuclease resistance in the triplex formation under physiological conditions, and may lead to progress in various triplex-formation-based strategies in vivo.
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interrupted 2 o 4 c aminomethylene bridged Nucleic Acid Modification enhances pyrimidine motif triplex forming ability and nuclease resistance under physiological condition
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, S Abdur M Rahman, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition
Nucleosides Nucleotides and Nucleic Acids, 2011Co-Authors: Hidetaka Torigoe, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hiroko Takuma, Kiyomi SasakiAbstract:Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical Modification, 2′-O,4′-C-aminomethylene bridged Nucleic Acid (2′,4′- BNANC) Modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC Modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC Modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC Modifications of TFO,...
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Promotion of triplex formation by 3′-amino-2′-O,4′-C-methylene bridged Nucleic Acid Modification
Nucleic Acids Symposium Series, 2009Co-Authors: Kiyomi Sasaki, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hidetaka TorigoeAbstract:We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid (3'-amino-2',4'-BNA) backbone Modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA Modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA Modification of TFO could be a key chemical Modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
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Promotion of triplex formation by 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid Modification.
Nucleic acids symposium series (2004), 2009Co-Authors: Kiyomi Sasaki, S. M. Abdur Rahman, Norihiro Sato, Satoshi Obika, Takeshi Imanishi, Hidetaka TorigoeAbstract:We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged Nucleic Acid (3'-amino-2',4'-BNA) backbone Modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA Modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA Modification of TFO could be a key chemical Modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
Takuma Katayama - One of the best experts on this subject based on the ideXlab platform.
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Synergistic Stabilization of Nucleic Acid Assembly by 2′-O,4′-C-Methylene-Bridged Nucleic Acid Modification and Additions of Comb-Type Cationic Copolymers†
Biochemistry, 2009Co-Authors: Hidetaka Torigoe, Satoshi Obika, Takeshi Imanishi, Atushi Maruyama, Takuma KatayamaAbstract:Stabilization of Nucleic Acid assemblies, such as duplex and triplex, is quite important for their wide variety of potential applications. Various stabilization methods, including molecular designs of chemically modified nucleotides and hybrid stabilizers, and combinations of different stabilization methods have been developed to increase stability of Nucleic Acid assemblies. However, combinations of two stabilizing methods have not always yielded desired synergistic effects. In the present study, to propose a strategy for selection of a rational combination of stabilizing methods, we demonstrate synergistic stabilization of triplex by 2′-O,4′-C-methylene-bridged Nucleic Acid (2′,4′-BNA) Modification of triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of these methods increased the binding constant for triplex formation by nearly 2 orders of magnitude. However, their kinetic contributions were quite d...
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synergistic stabilization of Nucleic Acid assembly by 2 o 4 c methylene bridged Nucleic Acid Modification and additions of comb type cationic copolymers
Biochemistry, 2009Co-Authors: Hidetaka Torigoe, Satoshi Obika, Takeshi Imanishi, Atushi Maruyama, Takuma KatayamaAbstract:Stabilization of Nucleic Acid assemblies, such as duplex and triplex, is quite important for their wide variety of potential applications. Various stabilization methods, including molecular designs of chemically modified nucleotides and hybrid stabilizers, and combinations of different stabilization methods have been developed to increase stability of Nucleic Acid assemblies. However, combinations of two stabilizing methods have not always yielded desired synergistic effects. In the present study, to propose a strategy for selection of a rational combination of stabilizing methods, we demonstrate synergistic stabilization of triplex by 2′-O,4′-C-methylene-bridged Nucleic Acid (2′,4′-BNA) Modification of triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of these methods increased the binding constant for triplex formation by nearly 2 orders of magnitude. However, their kinetic contributions were quite d...
