The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Christopher R. Bethel - One of the best experts on this subject based on the ideXlab platform.
-
Penem and penam sulfones and their reaction mechanisms.
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:(A) Chemical structures of penem and penam sulfone compounds. (B) proposed inhibition mechanism by a penem 1 (based on Knox’s work and others) [10], [11]; carbon atoms labeled with * are the stereo centers; (C) proposed reaction mechanism of SA1-204.
-
Penem 1 in SHV-1 active site. (
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:A) Stereo view of penem 1 interactions in SHV-1 active site. Hydrogen bonds are shown as dashed lines. (B) Stereo view of superpositioning of penem 1:SHV-1 (black) and penem 2:SHV-1 structures (grey). (C) Stereo view of superpositioning of penem 1:SHV-1 (black) and penem 2:GC1 β-lactamase (grey).
-
Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.
-
Structures of SHV-1 β-Lactamase with Penem and Penam Sulfone Inhibitors That Form Cyclic Intermediates Stabilized by Carbonyl Conjugation
2012Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Bacterial β-lactamase enzymes are in large part responsible for the decreased ability of β-lactam antibiotics to combat infections. The inability to overcome β-lactamase mediated resistance spurred the development of inhibitors with Penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, "suicide-type" inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of β-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine β-lactamases.
-
Structures of SHV-1 b-Lactamase with Penem and Penam Sulfone Inhibitors That Form Cyclic Intermediates Stabilized by Carbonyl Conjugation
2012Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Bacterial b-lactamase enzymes are in large part responsible for the decreased ability of b-lactam antibiotics to combat infections. The inability to overcome b-lactamase mediated resistance spurred the development of inhibitors with Penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, ‘‘suicide-type’ ’ inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of b-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-base
Timothy Gallagher - One of the best experts on this subject based on the ideXlab platform.
-
Thiocarbonyl-based 1,3-dipolarophiles for the
2015Co-Authors: Timothy Gallagher, Sylvie Sanchez, John H. Bateson, Peter JAbstract:synthesis of C(2)-unsubstituted Penems
-
thiocarbonyl based 1 3 dipolarophiles for the synthesis of c 2 unsubstituted Penems
2005Co-Authors: Timothy Gallagher, Sylvie Sanchez, John H. Bateson, Peter J OhanlonAbstract:The azomethine ylid strategy for β-lactam synthesis, which involves the fragmen- tation of a β-lactam-based oxazolidinone to give a carboxylated azomethine ylid, has been extended to the C(2)-unsubstituted penem scaffold associated with C(6)-exoalkylidene pen- ems. This involved the use of S-methyl dithioformate as a reactive 1,3-dipolarophile, which was most effectively employed by initial trapping with cyclopentadiene and subsequent re- generation of S-methyl dithioformate via a retro Diels-Alder reaction in the presence of the requisite oxazolidinone. This provided access to the penam scaffold, and this overall se- quence was very effectively accelerated by microwave irradiation. The synthesis of C(2)-un- substituted Penems was then accomplished by application of an oxidative elimination se- quence.
-
S-alkyl dithioformates as 1,3-dipolarophiles. Generation of C(2)-unsubstituted Penems.
2004Co-Authors: Sylvie Sanchez, John H. Bateson, Peter J. O'hanlon, Timothy GallagherAbstract:S-Alkyl dithioformates, generated by a cycloreversion process, react as 1,3-dipolarophiles with β-lactam-based azomethine ylids to provide, after (net) elimination of MeSH, C(2)-unsubstituted Penems. The overall cycloreversion/cycloaddition sequence was accelerated by microwave irradiation.
Sylvie Sanchez - One of the best experts on this subject based on the ideXlab platform.
-
Thiocarbonyl-based 1,3-dipolarophiles for the
2015Co-Authors: Timothy Gallagher, Sylvie Sanchez, John H. Bateson, Peter JAbstract:synthesis of C(2)-unsubstituted Penems
-
thiocarbonyl based 1 3 dipolarophiles for the synthesis of c 2 unsubstituted Penems
2005Co-Authors: Timothy Gallagher, Sylvie Sanchez, John H. Bateson, Peter J OhanlonAbstract:The azomethine ylid strategy for β-lactam synthesis, which involves the fragmen- tation of a β-lactam-based oxazolidinone to give a carboxylated azomethine ylid, has been extended to the C(2)-unsubstituted penem scaffold associated with C(6)-exoalkylidene pen- ems. This involved the use of S-methyl dithioformate as a reactive 1,3-dipolarophile, which was most effectively employed by initial trapping with cyclopentadiene and subsequent re- generation of S-methyl dithioformate via a retro Diels-Alder reaction in the presence of the requisite oxazolidinone. This provided access to the penam scaffold, and this overall se- quence was very effectively accelerated by microwave irradiation. The synthesis of C(2)-un- substituted Penems was then accomplished by application of an oxidative elimination se- quence.
-
S-alkyl dithioformates as 1,3-dipolarophiles. Generation of C(2)-unsubstituted Penems.
2004Co-Authors: Sylvie Sanchez, John H. Bateson, Peter J. O'hanlon, Timothy GallagherAbstract:S-Alkyl dithioformates, generated by a cycloreversion process, react as 1,3-dipolarophiles with β-lactam-based azomethine ylids to provide, after (net) elimination of MeSH, C(2)-unsubstituted Penems. The overall cycloreversion/cycloaddition sequence was accelerated by microwave irradiation.
Gianfranco Amicosante - One of the best experts on this subject based on the ideXlab platform.
-
Kinetic analysis of extension of substrate specificity with Xanthomonas maltophilia, Aeromonas hydrophila, and Bacillus cereus metallo-beta-lactamases.
1995Co-Authors: Antonio Felici, Gianfranco AmicosanteAbstract:Twenty beta-lactam molecules, including penicillins, cephalosporins, Penems, carbaPenems, and monobactams, were investigated as potential substrates for Xanthomonas maltophilia ULA-511, Aeromonas hydrophila AE036, and Bacillus cereus 5/B/6 metallo-beta-lactamases. A detailed analysis of the kinetic parameters examined confirmed these enzymes to be broad-spectrum beta-lactamases with different ranges of catalytic efficiency. Cefoxitin and moxalactam, substrates for the beta-lactamases from X. maltophilia ULA-511 and B. cereus 5/B/6, behaved as inactivators of the A. hydrophila AE036 metallo-beta-lactamase, which appeared to be unique among the enzymes tested in this study. In addition, we report a new, faster, and reliable purification procedure for the B. cereus 5/B/6 metallo-beta-lactamase, cloned in Escherichia coli HB101.
-
High specificity of cphA-encoded metallo-beta-lactamase from Aeromonas hydrophila AE036 for carbaPenems and its contribution to beta-lactam resistance.
1993Co-Authors: Bernardetta Segatore, Giuseppe Satta, Orietta Massidda, Domenico Setacci, Gianfranco AmicosanteAbstract:The Aeromonas hydrophila AE036 chromosome contains a cphA gene encoding a metallo-beta-lactamase highly active against carbapenem antibiotics. This enzyme was induced in strain AE036 to the same extent by both benzylpenicillin and imipenem. When the cphA gene was inserted into plasmid pACYC184, used to transform Escherichia coli DH5 alpha, the MICs of imipenem, meropenem, and penem HRE664 for recombinant clone DH5 alpha(pAA20R), expressing the Aeromonas metallo-beta-lactamase, were significantly increased, but those of penicillins and cephalosporins were not. When the metallo-beta-lactamase purified from E. coli DH5 alpha(pAA20R) was assayed with several beta-lactam substrates, it hydrolyzed carbaPenems but not penicillins or cephalosporins efficiently. These results demonstrate that this metallo-beta-lactamase possesses an unusual spectrum of activity compared with all the other class B enzymes identified so far, being active on Penems and carbaPenems only. This enzyme may thus contribute to the development of resistance to Penems and carbaPenems but not other beta-lactams.
Robert A. Bonomo - One of the best experts on this subject based on the ideXlab platform.
-
Penem and penam sulfones and their reaction mechanisms.
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:(A) Chemical structures of penem and penam sulfone compounds. (B) proposed inhibition mechanism by a penem 1 (based on Knox’s work and others) [10], [11]; carbon atoms labeled with * are the stereo centers; (C) proposed reaction mechanism of SA1-204.
-
Penem 1 in SHV-1 active site. (
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:A) Stereo view of penem 1 interactions in SHV-1 active site. Hydrogen bonds are shown as dashed lines. (B) Stereo view of superpositioning of penem 1:SHV-1 (black) and penem 2:SHV-1 structures (grey). (C) Stereo view of superpositioning of penem 1:SHV-1 (black) and penem 2:GC1 β-lactamase (grey).
-
Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.
2013Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.
-
Structures of SHV-1 β-Lactamase with Penem and Penam Sulfone Inhibitors That Form Cyclic Intermediates Stabilized by Carbonyl Conjugation
2012Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Bacterial β-lactamase enzymes are in large part responsible for the decreased ability of β-lactam antibiotics to combat infections. The inability to overcome β-lactamase mediated resistance spurred the development of inhibitors with Penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, "suicide-type" inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of β-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine β-lactamases.
-
Structures of SHV-1 b-Lactamase with Penem and Penam Sulfone Inhibitors That Form Cyclic Intermediates Stabilized by Carbonyl Conjugation
2012Co-Authors: Priyaranjan Pattanaik, Christopher R. Bethel, Anjaneyulu Sheri, John D. Buynak, Robert A. Bonomo, Focco Van Den AkkerAbstract:Bacterial b-lactamase enzymes are in large part responsible for the decreased ability of b-lactam antibiotics to combat infections. The inability to overcome b-lactamase mediated resistance spurred the development of inhibitors with Penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, ‘‘suicide-type’ ’ inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of b-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-base