The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Finian J. Leeper - One of the best experts on this subject based on the ideXlab platform.
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probing riboswitch ligand interactions using thiamine pyrophosphate analogues
Organic and Biomolecular Chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Jason Micklefield, Kwasi Agyeiowusu, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
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Probing riboswitch–ligand interactions using thiamine pyrophosphate analogues
Organic & biomolecular chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Kwasi Agyei-owusu, Jason Micklefield, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
Xiaoming Zhao - One of the best experts on this subject based on the ideXlab platform.
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Silver-promoted selective fluorination of 2-Aminopyrimidines: synthesis of 5-fluoro-2-Aminopyrimidine derivatives
Organic Chemistry Frontiers, 2019Co-Authors: Mingzhu Zhao, Juewang Cai, Xiaoming ZhaoAbstract:Selective fluorination of 4-substituted 2-Aminopyrimidine derivatives with Selectfluor in the presence of Ag2CO3 is presented. The substrates are 4-aryl- or vinyl- or amine-substituted 2-Aminopyrimidines. This method gives 4-substituted 5-fluoro-2-Aminopyrimidines in fair to high yields with excellent regioselectivities. 5-Fluoro-4-(pyridin-3-yl)-2-Aminopyrimidine was transformed into 5-fluoro-N-(2-methyl-5-nitrophenyl)-4-(pyridin-3-yl)pyrimidin-2-amine in the synthesis of fluorinated imatinib base.
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Ag-Assisted Fluorination of Unprotected 4,6-Disubstituted 2-Aminopyrimidines with Selectfluor.
The Journal of organic chemistry, 2017Co-Authors: Chenxi Wang, Juewang Cai, Min Zhang, Xiaoming ZhaoAbstract:A direct fluorination of 4,6-disubstituted 2-Aminopyrimidines with Selectfluor in the presence of Ag(I) is presented, affording the corresponding 4,6-disubstituted 5-fluoro-2-Aminopyrimidines with acceptable to high yield. Ag(I) is crucial for this chemoselective fluorination process. The transformation of 4,6-diphenyl 5-fluoro-2-Aminopyrimidine into N-(5-fluoro-4,6-diphenylpyrimidin-2-yl)-4-methylbenzenesulfonamide is discussed, and the reaction mechanism is investigated, as well.
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Ag-Assisted Fluorination of Unprotected 4,6-Disubstituted 2‑Aminopyrimidines with Selectfluor
2016Co-Authors: Chenxi Wang, Juewang Cai, Min Zhang, Xiaoming ZhaoAbstract:A direct fluorination of 4,6-disubstituted 2-Aminopyrimidines with Selectfluor in the presence of Ag(I) is presented, affording the corresponding 4,6-disubstituted 5-fluoro-2-Aminopyrimidines with acceptable to high yield. Ag(I) is crucial for this chemoselective fluorination process. The transformation of 4,6-diphenyl 5-fluoro-2-Aminopyrimidine into N-(5-fluoro-4,6-diphenylpyrimidin-2-yl)-4-methylbenzenesulfonamide is discussed, and the reaction mechanism is investigated, as well
Liuhong Chen - One of the best experts on this subject based on the ideXlab platform.
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probing riboswitch ligand interactions using thiamine pyrophosphate analogues
Organic and Biomolecular Chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Jason Micklefield, Kwasi Agyeiowusu, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
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Probing riboswitch–ligand interactions using thiamine pyrophosphate analogues
Organic & biomolecular chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Kwasi Agyei-owusu, Jason Micklefield, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
Chris Abell - One of the best experts on this subject based on the ideXlab platform.
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probing riboswitch ligand interactions using thiamine pyrophosphate analogues
Organic and Biomolecular Chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Jason Micklefield, Kwasi Agyeiowusu, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
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Probing riboswitch–ligand interactions using thiamine pyrophosphate analogues
Organic & biomolecular chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Kwasi Agyei-owusu, Jason Micklefield, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
Alison G. Smith - One of the best experts on this subject based on the ideXlab platform.
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probing riboswitch ligand interactions using thiamine pyrophosphate analogues
Organic and Biomolecular Chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Jason Micklefield, Kwasi Agyeiowusu, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
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Probing riboswitch–ligand interactions using thiamine pyrophosphate analogues
Organic & biomolecular chemistry, 2012Co-Authors: Liuhong Chen, Karl M. Erixon, Elena Cressina, Chris Abell, Alison G. Smith, Neil Dixon, Kwasi Agyei-owusu, Jason Micklefield, Finian J. LeeperAbstract:The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch–ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its Aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other Aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
