The Experts below are selected from a list of 350088 Experts worldwide ranked by ideXlab platform
L. S. Cederbaum - One of the best experts on this subject based on the ideXlab platform.
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a concerted synchronous 2 2 cycloreversion repair catalyzed by two electrons
Journal of Physical Chemistry Letters, 2018Co-Authors: Daly Davis, K. G. Bhushan, Y. Sajeev, L. S. CederbaumAbstract:The current understanding of photoenzyme-catalyzed [2 + 2] cycloreversion repair of cyclobutane pyrimidine dimer (CPD) is that a photogenerated electron from the photolyase enzyme catalyzes the repair. This one-electron catalyzed repair is a sequential two-bond breaking cycloreversion of the cyclobutane center and involves a negative ion radical as an intermediate. Here, by resonantly capturing two exogenous low-energy electrons into the Molecular Field of a CPD, we show that the concerted synchronous two-bond breaking reaction, which is intermediate-free, and hence a safe repair, is feasible through two-electron catalysis.
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A Concerted Synchronous [2 + 2] Cycloreversion Repair Catalyzed by Two Electrons
2018Co-Authors: Daly Davis, K. G. Bhushan, Y. Sajeev, L. S. CederbaumAbstract:The current understanding of photoenzyme-catalyzed [2 + 2] cycloreversion repair of cyclobutane pyrimidine dimer (CPD) is that a photogenerated electron from the photolyase enzyme catalyzes the repair. This one-electron catalyzed repair is a sequential two-bond breaking cycloreversion of the cyclobutane center and involves a negative ion radical as an intermediate. Here, by resonantly capturing two exogenous low-energy electrons into the Molecular Field of a CPD, we show that the concerted synchronous two-bond breaking reaction, which is intermediate-free, and hence a safe repair, is feasible through two-electron catalysis
Peter Thomas - One of the best experts on this subject based on the ideXlab platform.
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comparison between steroid binding to membrane progesterone receptor α mprα and to nuclear progesterone receptor correlation with physicochemical properties assessed by comparative Molecular Field analysis and identification of mprα specific agonists
Steroids, 2010Co-Authors: Jan Kelder, Rita Azevedo, Yefei Pang, Jing Dong, Jacob De Vlieg, Peter ThomasAbstract:Recent results showing that the binding characteristics of 33 steroids for human membrane progesterone receptor alpha (hu-mPRalpha) differ from those for the nuclear progesterone receptor (nPR) suggest that hu-mPRalpha-specific agonists can be identified for investigating its physiological functions. The binding affinities of an additional 21 steroids for hu-mPRalpha were determined to explore the structure-activity relationships in more detail and to identify potent, specific mPRalpha agonists. Four synthetic progesterone derivatives with methyl or methylene groups on positions 18 or 19, 18a-methylprogesterone (18-CH(3)P4, Org OE 64-0), 13-ethenyl-18-norprogesterone (18-CH(2)P4, Org 33663-0), 19a-methylprogesterone (19-CH(3)P4, Org OD 13-0) and 10-ethenyl-19-norprogesterone (19-CH(2)P4, Org OD 02-0), showed similar or higher affinities than progesterone for hu-mPRalpha and displayed mPRalpha agonist activities in G-protein and MAP kinase activation assays. All four steroids also bound to the nPR in cytosolic fractions of MCF-7 cells. However, two compounds, 19-CH(2)P4 and 19-CH(3)P4, showed no nPR agonist activity in a nPR reporter assay and therefore are selective mPRalpha agonists suitable for physiological investigations. The structure-binding relationships of the combined series of 54 steroids for hu-mPRalpha deviated strikingly from those of a published set of 60 3-keto or 3-desoxy steroids for nPR. Close correlations were observed between the receptor binding affinities of the steroids and their physicochemical properties calculated by comparative Molecular Field analysis (CoMFA) for both hu-mPRalpha and nPR. A comparison of the CoMFA Field graphs for the two receptors revealed several differences in the structural features required for binding to hu-mPRalpha and nPR which could be exploited to develop additional mPR-specific ligands.
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comparison between steroid binding to progesterone membrane receptor α mprα and to progesterone nuclear receptor correlation with physicochemical properties assessed by comparative Molecular Field analysis and identification of mprα specific agonists
Steroids, 2010Co-Authors: Jan Kelder, Rita Azevedo, Yefei Pang, Jing Dong, Jacob De Vlieg, Peter ThomasAbstract:Recent results showing that the binding characteristics of 33 steroids for human membrane progesterone receptor alpha (hu-mPRα) differ from those for the nuclear progesterone receptor (nPR) suggest that hu-mPRα-specific agonists can be identified for investigating its physiological functions. The binding affinities of an additional 21 steroids for hu-mPRα were determined to explore the structure-activity relationships in more detail and to identify potent, specific mPRα agonists. Four synthetic progesterone derivatives with methyl or methylene groups on positions 18 or 19, 18a-methylprogesterone (18-CH3P4, Org OE 64-0), 13-ethenyl-18-norprogesterone (18-CH2P4, Org 33663-0), 19a-methylprogesterone (19-CH3P4, Org OD 13-0) and 10-ethenyl-19-norprogesterone (19-CH2P4, Org OD 02-0), showed similar or higher affinities than progesterone for hu-mPRα and displayed mPRα agonist activities in G-protein and MAP kinase activation assays. All four steroids also bound to the nPR in cytosolic fractions of MCF-7 cells. However, two compounds, 19-CH2P4 and 19-CH3P4, showed no nPR agonist activity in a nPR reporter assay and therefore are selective mPRα agonists suitable for physiological investigations. The structure-binding relationships of the combined series of 54 steroids for hu-mPRα deviated strikingly from those of a published set of 60 3-keto or 3-desoxy steroids for nPR. Close correlations were observed between the receptor binding affinities of the steroids and their physicochemical properties calculated by comparative Molecular Field analysis (CoMFA) for both hu-mPRα and nPR. A comparison of the CoMFA Field graphs for the two receptors revealed several differences in the structural features required for binding to hu-mPRα and nPR which could be exploited to develop additional mPR-specific ligands.
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comparison between steroid binding to membrane progesterone receptor alpha mpralpha and to nuclear progesterone receptor correlation with physicochemical properties assessed by comparative Molecular Field analysis and identification of mpralpha specific agonists
Steroids, 2010Co-Authors: Jan Kelder, Rita Azevedo, Yefei Pang, De Vlieg J, Jing Dong, Peter ThomasAbstract:Recent results showing that the binding characteristics of 33 steroids for human membrane progesterone receptor alpha (hu-mPRalpha) differ from those for the nuclear progesterone receptor (nPR) suggest that hu-mPRalpha-specific agonists can be identified for investigating its physiological functions. The binding affinities of an additional 21 steroids for hu-mPRalpha were determined to explore the structure-activity relationships in more detail and to identify potent, specific mPRalpha agonists. Four synthetic progesterone derivatives with methyl or methylene groups on positions 18 or 19, 18a-methylprogesterone (18-CH(3)P4, Org OE 64-0), 13-ethenyl-18-norprogesterone (18-CH(2)P4, Org 33663-0), 19a-methylprogesterone (19-CH(3)P4, Org OD 13-0) and 10-ethenyl-19-norprogesterone (19-CH(2)P4, Org OD 02-0), showed similar or higher affinities than progesterone for hu-mPRalpha and displayed mPRalpha agonist activities in G-protein and MAP kinase activation assays. All four steroids also bound to the nPR in cytosolic fractions of MCF-7 cells. However, two compounds, 19-CH(2)P4 and 19-CH(3)P4, showed no nPR agonist activity in a nPR reporter assay and therefore are selective mPRalpha agonists suitable for physiological investigations. The structure-binding relationships of the combined series of 54 steroids for hu-mPRalpha deviated strikingly from those of a published set of 60 3-keto or 3-desoxy steroids for nPR. Close correlations were observed between the receptor binding affinities of the steroids and their physicochemical properties calculated by comparative Molecular Field analysis (CoMFA) for both hu-mPRalpha and nPR. A comparison of the CoMFA Field graphs for the two receptors revealed several differences in the structural features required for binding to hu-mPRalpha and nPR which could be exploited to develop additional mPR-specific ligands.
Daly Davis - One of the best experts on this subject based on the ideXlab platform.
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a concerted synchronous 2 2 cycloreversion repair catalyzed by two electrons
Journal of Physical Chemistry Letters, 2018Co-Authors: Daly Davis, K. G. Bhushan, Y. Sajeev, L. S. CederbaumAbstract:The current understanding of photoenzyme-catalyzed [2 + 2] cycloreversion repair of cyclobutane pyrimidine dimer (CPD) is that a photogenerated electron from the photolyase enzyme catalyzes the repair. This one-electron catalyzed repair is a sequential two-bond breaking cycloreversion of the cyclobutane center and involves a negative ion radical as an intermediate. Here, by resonantly capturing two exogenous low-energy electrons into the Molecular Field of a CPD, we show that the concerted synchronous two-bond breaking reaction, which is intermediate-free, and hence a safe repair, is feasible through two-electron catalysis.
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A Concerted Synchronous [2 + 2] Cycloreversion Repair Catalyzed by Two Electrons
2018Co-Authors: Daly Davis, K. G. Bhushan, Y. Sajeev, L. S. CederbaumAbstract:The current understanding of photoenzyme-catalyzed [2 + 2] cycloreversion repair of cyclobutane pyrimidine dimer (CPD) is that a photogenerated electron from the photolyase enzyme catalyzes the repair. This one-electron catalyzed repair is a sequential two-bond breaking cycloreversion of the cyclobutane center and involves a negative ion radical as an intermediate. Here, by resonantly capturing two exogenous low-energy electrons into the Molecular Field of a CPD, we show that the concerted synchronous two-bond breaking reaction, which is intermediate-free, and hence a safe repair, is feasible through two-electron catalysis
Arthur M Doweyko - One of the best experts on this subject based on the ideXlab platform.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative Molecular Field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric antisecretory activity using comparative Molecular Field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive Molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K(+)-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence on determining biological activity were consistent and complementary to each other.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative Molecular Field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric antisecretory activity using comparative Molecular Field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive Molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K+-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K+-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence...
Irving W Wainer - One of the best experts on this subject based on the ideXlab platform.
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comparative Molecular Field analysis of fenoterol derivatives interacting with an agonist stabilized form of the β2 adrenergic receptor
Bioorganic & Medicinal Chemistry, 2014Co-Authors: Anita Plazinska, Karolina Pajak, Ewelina Rutkowska, Lucita Jimenez, Joseph A Kozocas, Gary Koolpe, Mary J Tanga, Lawrence Toll, Irving W Wainer, Krzysztof JozwiakAbstract:The β2-adrenergic receptor (β2-AR) agonist [3H]-(R,R′)-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (Ki values) of the stereoisomers of a series of 4′-methoxyfenoterol analogs in which the length of the alkyl substituent at α′ position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [3H]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the β2-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the α′ position. The results also indicate that the Ki values obtained using [3H]-(R,R′)-methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [3H]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the β2-AR conformation probed by [3H]-(R,R′)-4′-methoxyfenoterol. The CoMFA model of the agonist-stabilized β2-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the β2-AR is governed to a greater extend by steric effects than binding to the [3H]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role.
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comparative Molecular Field analysis of fenoterol derivatives a platform towards highly selective and effective β2 adrenergic receptor agonists
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Krzysztof Jozwiak, Anita Plazinska, Lucita Jimenez, Joseph A Kozocas, Mary J Tanga, Lawrence Toll, Anthony Yiuho Woo, Ruiping Xiao, Irving W WainerAbstract:Purpose to use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the β2 adrenergic receptor.
