The Experts below are selected from a list of 43824 Experts worldwide ranked by ideXlab platform
David J. Craik - One of the best experts on this subject based on the ideXlab platform.
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How bugs make lassos
Chemistry & biology, 2009Co-Authors: K. Johan Rosengren, David J. CraikAbstract:In this issue of Chemistry & Biology, Knappe et al. report the generation of a series of mutants of the Bacterial Peptide capistruin to help unravel key aspects of the biosynthesis of its unusual lasso structure.
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microcin j25 has a threaded sidechain to backbone ring structure and not a head to tail cyclized backbone
Journal of the American Chemical Society, 2003Co-Authors: Johan K Rosengren, Richard J Clark, Norelle L Daly, Ulf Goransson, And Alun Jones, David J. CraikAbstract:Microcin J25 is a 21 amino acid Bacterial Peptide that has potent antiBacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The Peptide was previously proposed to have a head-to-tail cyclized Peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747−755). It exhibits remarkable thermal stability for a Peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the Peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is p...
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microcin j25 has a threaded sidechain to backbone ring structure and not a head to tail cyclized backbone
Journal of the American Chemical Society, 2003Co-Authors: Johan K Rosengren, Richard J Clark, Norelle L Daly, Ulf Goransson, And Alun Jones, David J. CraikAbstract:Microcin J25 is a 21 amino acid Bacterial Peptide that has potent antiBacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The Peptide was previously proposed to have a head-to-tail cyclized Peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747-755). It exhibits remarkable thermal stability for a Peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the Peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is prevented by two aromatic residues flanking the embedded ring. Unthreading does not occur even when the molecule is enzymatically digested with thermolysin. The new structural interpretation fully accounts for previously reported NMR and biophysical data and is consistent with the remarkable stability of this potent antimicrobial Peptide.
Philip Cohen - One of the best experts on this subject based on the ideXlab platform.
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Activation of the neutrophil NADPH oxidase is inhibited by SB 203580, a specific inhibitor of SAPK2/p38.
Biochemical and Biophysical Research Communications, 1999Co-Authors: Aroon S. Lal, Andrew Clifton, John Rouse, Anthony W. Segal, Philip CohenAbstract:Activation of the neutrophil NADPH oxidase by either the Bacterial Peptide fMLP or phorbol myristate acetate (PMA) is partially suppressed by SB 203580, a specific inhibitor of the MAP kinase family member, SAPK2/p38. The concentration of SB 203580 that suppresses activation of NADPH oxidase is similar to that which inhibits SAPK2/p38 in vitro, and both fMLP and PMA induce an extremely rapid and potent activation of SAPK2/p38 in neutrophils. SB 203580 does not exert its effect by preventing the neutrophil priming reaction, by suppressing the phosphorylation of p47phax, or by preventing the translocation of p47phax/p67phax to the plasma membrane.
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activation of the neutrophil nadph oxidase is inhibited by sb 203580 a specific inhibitor of sapk2 p38
Biochemical and Biophysical Research Communications, 1999Co-Authors: Aroon S. Lal, Andrew Clifton, John Rouse, Anthony W. Segal, Philip CohenAbstract:Activation of the neutrophil NADPH oxidase by either the Bacterial Peptide fMLP or phorbol myristate acetate (PMA) is partially suppressed by SB 203580, a specific inhibitor of the MAP kinase family member, SAPK2/p38. The concentration of SB 203580 that suppresses activation of NADPH oxidase is similar to that which inhibits SAPK2/p38 in vitro, and both fMLP and PMA induce an extremely rapid and potent activation of SAPK2/p38 in neutrophils. SB 203580 does not exert its effect by preventing the neutrophil priming reaction, by suppressing the phosphorylation of p47phax, or by preventing the translocation of p47phax/p67phax to the plasma membrane.
Aroon S. Lal - One of the best experts on this subject based on the ideXlab platform.
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Activation of the neutrophil NADPH oxidase is inhibited by SB 203580, a specific inhibitor of SAPK2/p38.
Biochemical and Biophysical Research Communications, 1999Co-Authors: Aroon S. Lal, Andrew Clifton, John Rouse, Anthony W. Segal, Philip CohenAbstract:Activation of the neutrophil NADPH oxidase by either the Bacterial Peptide fMLP or phorbol myristate acetate (PMA) is partially suppressed by SB 203580, a specific inhibitor of the MAP kinase family member, SAPK2/p38. The concentration of SB 203580 that suppresses activation of NADPH oxidase is similar to that which inhibits SAPK2/p38 in vitro, and both fMLP and PMA induce an extremely rapid and potent activation of SAPK2/p38 in neutrophils. SB 203580 does not exert its effect by preventing the neutrophil priming reaction, by suppressing the phosphorylation of p47phax, or by preventing the translocation of p47phax/p67phax to the plasma membrane.
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activation of the neutrophil nadph oxidase is inhibited by sb 203580 a specific inhibitor of sapk2 p38
Biochemical and Biophysical Research Communications, 1999Co-Authors: Aroon S. Lal, Andrew Clifton, John Rouse, Anthony W. Segal, Philip CohenAbstract:Activation of the neutrophil NADPH oxidase by either the Bacterial Peptide fMLP or phorbol myristate acetate (PMA) is partially suppressed by SB 203580, a specific inhibitor of the MAP kinase family member, SAPK2/p38. The concentration of SB 203580 that suppresses activation of NADPH oxidase is similar to that which inhibits SAPK2/p38 in vitro, and both fMLP and PMA induce an extremely rapid and potent activation of SAPK2/p38 in neutrophils. SB 203580 does not exert its effect by preventing the neutrophil priming reaction, by suppressing the phosphorylation of p47phax, or by preventing the translocation of p47phax/p67phax to the plasma membrane.
Johan K Rosengren - One of the best experts on this subject based on the ideXlab platform.
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microcin j25 has a threaded sidechain to backbone ring structure and not a head to tail cyclized backbone
Journal of the American Chemical Society, 2003Co-Authors: Johan K Rosengren, Richard J Clark, Norelle L Daly, Ulf Goransson, And Alun Jones, David J. CraikAbstract:Microcin J25 is a 21 amino acid Bacterial Peptide that has potent antiBacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The Peptide was previously proposed to have a head-to-tail cyclized Peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747−755). It exhibits remarkable thermal stability for a Peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the Peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is p...
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microcin j25 has a threaded sidechain to backbone ring structure and not a head to tail cyclized backbone
Journal of the American Chemical Society, 2003Co-Authors: Johan K Rosengren, Richard J Clark, Norelle L Daly, Ulf Goransson, And Alun Jones, David J. CraikAbstract:Microcin J25 is a 21 amino acid Bacterial Peptide that has potent antiBacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The Peptide was previously proposed to have a head-to-tail cyclized Peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747-755). It exhibits remarkable thermal stability for a Peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the Peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is prevented by two aromatic residues flanking the embedded ring. Unthreading does not occur even when the molecule is enzymatically digested with thermolysin. The new structural interpretation fully accounts for previously reported NMR and biophysical data and is consistent with the remarkable stability of this potent antimicrobial Peptide.
Jaiprakash N. Sangshetti - One of the best experts on this subject based on the ideXlab platform.
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Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study.
Archiv der Pharmazie, 2016Co-Authors: Firoz A.kalam Khan, Rohidas B. Arote, Devanand B Shinde, Rajendra Patil, Manjiri Patil, Jaiprakash N. SangshettiAbstract:The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a-l as Bacterial Peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC50 value = 5.50 μM) and 7g (IC50 value = 7.25 μM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75-11.66 μg/mL) and 7g (MIC range = 8.91-12.83 μg/mL) also showed potent antiBacterial activity when compared with the standard ciprofloxacin (MIC range = 25-50 μg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antiBacterial agents. In order to gain more insight into the binding mode of the compounds with the PDF enzyme, the most active compounds 7e and 7g, the moderately active compound 7k, and the least active compound 7h were docked against the PDF enzyme of Escherichia coli. The docking study of the most active compounds 7e and 7g against the PDF enzyme exhibited good binding properties. Hence, we believe our synthesized compounds 7a-l could serve as reservoir for Bacterial PDF inhibitor development.
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Design and synthesis of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as Bacterial Peptide deformylase inhibitors.
Chemical biology & drug design, 2016Co-Authors: Firoz A.kalam Khan, Devanand B Shinde, Rajendra Patil, Jaiprakash N. SangshettiAbstract:Herein, we report the synthesis and screening of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a-j) as Bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value = 139.28 μm), 11g (IC50 value = 136.18 μm), and 11h (IC50 value = 131.65 μm) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36-167.26 μg/mL), 11g (MIC range = 93.75-145.67 μg/mL), and 11h (MIC range = 63.61-126.63 μg/mL) had also shown potent antiBacterial activity when compared with standard ampicillin (MIC range = 100.00-250.00 μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antiBacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a-j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antiBacterial drugs.
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Biphenyl tetrazole-thiazolidinediones as novel Bacterial Peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study
Biomedicine and Pharmacotherapy, 2016Co-Authors: Firoz A.kalam Khan, Kaivalya S. Jadhav, Rohidas B. Arote, Rajendra H. Patil, Devanand B Shinde, Jaiprakash N. SangshettiAbstract:Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as Bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC50 value = 16.25 μM), 14c (IC50 value = 18.00 μM) and 14h (IC50 value = 17.25 μM) had shown good PDF inhibition activity. The compounds 14b (MIC range = 20.75–35.41 μg/mL), 14c (MIC range = 19.41–26.00 μg/mL) and 14d (MIC range = 8.41–8.58 μg/mL) had also shown potent antiBacterial activity when compared with standard ciprofloxacin (MIC range = 25–50 μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antiBacterial agents. In order to gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antiBacterial drugs.