The Experts below are selected from a list of 5349 Experts worldwide ranked by ideXlab platform
Adam Kraszewski - One of the best experts on this subject based on the ideXlab platform.
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Aryl h-phosphonates. 14. Synthesis of new nucleotide analogues with phosphonate-Phosphate internucleosidic linkage.
Organic letters, 2003Co-Authors: Marzena Szymczak, Agnieszka Szymanska, Jacek Stawinski, Jerzy Boryski, Adam KraszewskiAbstract:[reaction: see text] Aryl Nucleoside H-phosphonates 3 and aryl Nucleoside P-acylphosphonates 4, generated in situ from the appropriate H-phosphonate 1 and acylphosphonate monoesters 2, respectively, reacted rapidly in the presence of tertiary amines to produce in high yields the extended, pyroPhosphate analogues, diaryl diNucleoside phosphonate-Phosphate derivatives 6. These, depending on a substituent on the alpha-carbon of the phosphonate moiety, either underwent transformation into the diNucleoside phosphonate-Phosphate 7 or afforded Nucleoside H-phosphonates 8 and aryl Nucleoside Phosphate 9.
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aryl h phosphonates part 13 a new general entry to aryl Nucleoside Phosphate and aryl Nucleoside phosphorothioate diesters
Journal of The Chemical Society-perkin Transactions 1, 2002Co-Authors: Jacek Cieślak, Jacek Stawinski, Jadwiga Jankowska, Michal Sobkowski, Malgorzata Wenska, Adam KraszewskiAbstract:The reaction of Nucleoside H-phosphonate monoesters with phenols in the presence of a condensing agent, followed by oxidation of the in-situ-generated aryl Nucleoside H-phosphonate diesters with iodine–water or with elemental sulfur, provides a new, ‘one-pot’, efficient entry to Nucleoside Phosphate or Nucleoside phosphorothioate diesters bearing diverse aryl moieties.
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Nucleoside Phosphate analogues of biological interest and their synthesis via aryl Nucleoside h phosphonates as intermediates
Acta Biochimica Polonica, 2001Co-Authors: Jacek Cieślak, Marzena Szymczak, Jacek Stawinski, Jadwiga Jankowska, Michal Sobkowski, Malgorzata Wenska, Barbara Imiolczyk, Izabela Zagorowska, David Shugar, Adam KraszewskiAbstract:This review presents a brief account of the chemistry and mechanistic aspects of aryl H-phosphonates, and selected applications of this class of compounds as intermediates in the synthesis of a wide range of biologically important analogues of Nucleoside Phosphates, and oligonucleotides, in which the Phosphate moieties are replaced by other structurally related groups. The aryl Nucleoside H-phosphonates, compounds of controlled reactivity, have proven to be more versatile and superior to various mixed anhydrides as synthetic intermediates, particularly for preparation of nucleotide analogues bearing P-N or P-S bonds in various configurational arrangements at the Phosphate moiety.
Stephen J Butler - One of the best experts on this subject based on the ideXlab platform.
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a simple robust universal assay for real time enzyme monitoring by signalling changes in Nucleoside Phosphate anion concentration using a europium iii based anion receptor
Chemical Science, 2019Co-Authors: Sarah H Hewitt, Romain Mailhot, Rozee Ali, Chloe R. Antonen, Charlotte A. Dodson, Stephen J ButlerAbstract:Enzymes that consume and produce Nucleoside polyPhosphate (NPP) anions represent major targets in drug discovery. For example, protein kinases are one of the largest classes of drug targets in the fight against cancer. The accurate determination of enzyme kinetics and mechanisms is a critical aspect of drug discovery research. To increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical researchers have robust, affordable assays to measure enzyme activity accurately. We present a simple, sensitive microplate assay for real-time monitoring of a range of pharmaceutically important enzyme reactions that generate NPP anions, including kinases and glycosyltransferases. Our assay utilises a single, stable europium(iii) complex that binds reversibly to NPP anions, signalling the dynamic changes in NPP product/substrate ratio during an enzyme reaction using time-resolved luminescence. This supramolecular approach to enzyme monitoring overcomes significant limitations in existing assays, obviating the need for expensive antibodies or equipment, chemically labelled substrates or products and isolation or purification steps. Our label and antibody-free method enables rapid and quantitative analysis of enzyme activities and inhibition, offering a potentially powerful tool for use in drug discovery, suitable for high-throughput screening of inhibitors and accurate measurements of enzyme kinetic parameters.
Sarah H Hewitt - One of the best experts on this subject based on the ideXlab platform.
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Tuning the anion binding properties of lanthanide receptors to discriminate Nucleoside Phosphates in a sensing array
2020Co-Authors: Sarah H Hewitt, Georgina Macey, Romain Mailhot, Mark Elsegood, Fernanda Duarte, Alan M Kenwright, Stephen ButlerAbstract:The development of synthetic receptors for the selective binding and discrimination of anions in water requires an understanding of how anions interact with these synthetic receptors. Molecules designed to differentiate Nucleoside Phosphate anions (e.g. ATP, ADP, GTP, GDP, UDP) under physiological conditions could underpin exciting new sensing tools for biomedical research and drug discovery, but it is very challenging due to the similarities in anion structure, size and charge. We present a series of lanthanide-based anion receptors and establish key structural elements that impact on Nucleoside Phosphate anion binding and sensing. Structural evidence of anion binding using X-ray crystallographic and NMR data, supported by DFT calculations indicate the binding modes between the lanthanide complexes and certain phosphoanions, revealing a bidentate (α-, γ-) binding mode to ATP. We further use four of the receptors to allow discrimination of eight Nucleoside Phosphate anions in the first array-based assay using lanthanide complexes, taking advantage of the multiple emission bands and long emission lifetimes associated with luminescent lanthanide complexes.
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a simple robust universal assay for real time enzyme monitoring by signalling changes in Nucleoside Phosphate anion concentration using a europium iii based anion receptor
Chemical Science, 2019Co-Authors: Sarah H Hewitt, Romain Mailhot, Rozee Ali, Chloe R. Antonen, Charlotte A. Dodson, Stephen J ButlerAbstract:Enzymes that consume and produce Nucleoside polyPhosphate (NPP) anions represent major targets in drug discovery. For example, protein kinases are one of the largest classes of drug targets in the fight against cancer. The accurate determination of enzyme kinetics and mechanisms is a critical aspect of drug discovery research. To increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical researchers have robust, affordable assays to measure enzyme activity accurately. We present a simple, sensitive microplate assay for real-time monitoring of a range of pharmaceutically important enzyme reactions that generate NPP anions, including kinases and glycosyltransferases. Our assay utilises a single, stable europium(iii) complex that binds reversibly to NPP anions, signalling the dynamic changes in NPP product/substrate ratio during an enzyme reaction using time-resolved luminescence. This supramolecular approach to enzyme monitoring overcomes significant limitations in existing assays, obviating the need for expensive antibodies or equipment, chemically labelled substrates or products and isolation or purification steps. Our label and antibody-free method enables rapid and quantitative analysis of enzyme activities and inhibition, offering a potentially powerful tool for use in drug discovery, suitable for high-throughput screening of inhibitors and accurate measurements of enzyme kinetic parameters.
Jacek Stawinski - One of the best experts on this subject based on the ideXlab platform.
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Aryl h-phosphonates. 14. Synthesis of new nucleotide analogues with phosphonate-Phosphate internucleosidic linkage.
Organic letters, 2003Co-Authors: Marzena Szymczak, Agnieszka Szymanska, Jacek Stawinski, Jerzy Boryski, Adam KraszewskiAbstract:[reaction: see text] Aryl Nucleoside H-phosphonates 3 and aryl Nucleoside P-acylphosphonates 4, generated in situ from the appropriate H-phosphonate 1 and acylphosphonate monoesters 2, respectively, reacted rapidly in the presence of tertiary amines to produce in high yields the extended, pyroPhosphate analogues, diaryl diNucleoside phosphonate-Phosphate derivatives 6. These, depending on a substituent on the alpha-carbon of the phosphonate moiety, either underwent transformation into the diNucleoside phosphonate-Phosphate 7 or afforded Nucleoside H-phosphonates 8 and aryl Nucleoside Phosphate 9.
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aryl h phosphonates part 13 a new general entry to aryl Nucleoside Phosphate and aryl Nucleoside phosphorothioate diesters
Journal of The Chemical Society-perkin Transactions 1, 2002Co-Authors: Jacek Cieślak, Jacek Stawinski, Jadwiga Jankowska, Michal Sobkowski, Malgorzata Wenska, Adam KraszewskiAbstract:The reaction of Nucleoside H-phosphonate monoesters with phenols in the presence of a condensing agent, followed by oxidation of the in-situ-generated aryl Nucleoside H-phosphonate diesters with iodine–water or with elemental sulfur, provides a new, ‘one-pot’, efficient entry to Nucleoside Phosphate or Nucleoside phosphorothioate diesters bearing diverse aryl moieties.
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Nucleoside Phosphate analogues of biological interest and their synthesis via aryl Nucleoside h phosphonates as intermediates
Acta Biochimica Polonica, 2001Co-Authors: Jacek Cieślak, Marzena Szymczak, Jacek Stawinski, Jadwiga Jankowska, Michal Sobkowski, Malgorzata Wenska, Barbara Imiolczyk, Izabela Zagorowska, David Shugar, Adam KraszewskiAbstract:This review presents a brief account of the chemistry and mechanistic aspects of aryl H-phosphonates, and selected applications of this class of compounds as intermediates in the synthesis of a wide range of biologically important analogues of Nucleoside Phosphates, and oligonucleotides, in which the Phosphate moieties are replaced by other structurally related groups. The aryl Nucleoside H-phosphonates, compounds of controlled reactivity, have proven to be more versatile and superior to various mixed anhydrides as synthetic intermediates, particularly for preparation of nucleotide analogues bearing P-N or P-S bonds in various configurational arrangements at the Phosphate moiety.
Romain Mailhot - One of the best experts on this subject based on the ideXlab platform.
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Tuning the anion binding properties of lanthanide receptors to discriminate Nucleoside Phosphates in a sensing array
2020Co-Authors: Sarah H Hewitt, Georgina Macey, Romain Mailhot, Mark Elsegood, Fernanda Duarte, Alan M Kenwright, Stephen ButlerAbstract:The development of synthetic receptors for the selective binding and discrimination of anions in water requires an understanding of how anions interact with these synthetic receptors. Molecules designed to differentiate Nucleoside Phosphate anions (e.g. ATP, ADP, GTP, GDP, UDP) under physiological conditions could underpin exciting new sensing tools for biomedical research and drug discovery, but it is very challenging due to the similarities in anion structure, size and charge. We present a series of lanthanide-based anion receptors and establish key structural elements that impact on Nucleoside Phosphate anion binding and sensing. Structural evidence of anion binding using X-ray crystallographic and NMR data, supported by DFT calculations indicate the binding modes between the lanthanide complexes and certain phosphoanions, revealing a bidentate (α-, γ-) binding mode to ATP. We further use four of the receptors to allow discrimination of eight Nucleoside Phosphate anions in the first array-based assay using lanthanide complexes, taking advantage of the multiple emission bands and long emission lifetimes associated with luminescent lanthanide complexes.
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a simple robust universal assay for real time enzyme monitoring by signalling changes in Nucleoside Phosphate anion concentration using a europium iii based anion receptor
Chemical Science, 2019Co-Authors: Sarah H Hewitt, Romain Mailhot, Rozee Ali, Chloe R. Antonen, Charlotte A. Dodson, Stephen J ButlerAbstract:Enzymes that consume and produce Nucleoside polyPhosphate (NPP) anions represent major targets in drug discovery. For example, protein kinases are one of the largest classes of drug targets in the fight against cancer. The accurate determination of enzyme kinetics and mechanisms is a critical aspect of drug discovery research. To increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical researchers have robust, affordable assays to measure enzyme activity accurately. We present a simple, sensitive microplate assay for real-time monitoring of a range of pharmaceutically important enzyme reactions that generate NPP anions, including kinases and glycosyltransferases. Our assay utilises a single, stable europium(iii) complex that binds reversibly to NPP anions, signalling the dynamic changes in NPP product/substrate ratio during an enzyme reaction using time-resolved luminescence. This supramolecular approach to enzyme monitoring overcomes significant limitations in existing assays, obviating the need for expensive antibodies or equipment, chemically labelled substrates or products and isolation or purification steps. Our label and antibody-free method enables rapid and quantitative analysis of enzyme activities and inhibition, offering a potentially powerful tool for use in drug discovery, suitable for high-throughput screening of inhibitors and accurate measurements of enzyme kinetic parameters.
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A simple, robust, universal assay for real-time enzyme monitoring by signalling changes in Nucleoside Phosphate anion concentration using a europium(III)-based anion receptor
2019Co-Authors: Sarah Hewitt, Romain Mailhot, Rozee Ali, Chloe R. Antonen, Charlotte A. Dodson, Stephen ButlerAbstract:© 2019 The Royal Society of Chemistry. Enzymes that consume and produce Nucleoside polyPhosphate (NPP) anions represent major targets in drug discovery. For example, protein kinases are one of the largest classes of drug targets in the fight against cancer. The accurate determination of enzyme kinetics and mechanisms is a critical aspect of drug discovery research. To increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical researchers have robust, affordable assays to measure enzyme activity accurately. We present a simple, sensitive microplate assay for real-time monitoring of a range of pharmaceutically important enzyme reactions that generate NPP anions, including kinases and glycosyltransferases. Our assay utilises a single, stable europium(iii) complex that binds reversibly to NPP anions, signalling the dynamic changes in NPP product/substrate ratio during an enzyme reaction using time-resolved luminescence. This supramolecular approach to enzyme monitoring overcomes significant limitations in existing assays, obviating the need for expensive antibodies or equipment, chemically labelled substrates or products and isolation or purification steps. Our label and antibody-free method enables rapid and quantitative analysis of enzyme activities and inhibition, offering a potentially powerful tool for use in drug discovery, suitable for high-throughput screening of inhibitors and accurate measurements of enzyme kinetic parameters
