Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process
Herein, we describe the use of thioglycosides as glycosidase inhibitors by employing novel modifications at the reducing end of these glycomimetics. The inhibitors display a basic galactopyranosyl unit (1→4)-bonded to a 3-deoxy-4-thiopentopyranose moiety. The molecular basis of the observed inhibiti...
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2013
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paper:paper_09476539_v19_n13_p4262_Calle2023-06-08T15:53:57Z Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process conformation analysis enzyme models glycosides NMR spectroscopy S ligands Conformation analysis Conformational selection Enzyme models Experimental evidence Glycosidase inhibitors Ground-state conformations Molecular modeling techniques S ligands Chemical compounds Escherichia coli Glycosides Ligands Molecular recognition Nuclear magnetic resonance spectroscopy Van der Waals forces Conformations benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D erythro pentopyranoside benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D threo pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-erythro-pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-threo-pentopyranoside beta galactosidase disaccharide ligand thioglycoside article chemical structure chemistry drug antagonism enzymology Escherichia coli nuclear magnetic resonance spectroscopy beta-Galactosidase Disaccharides Escherichia coli Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Structure Thioglucosides Herein, we describe the use of thioglycosides as glycosidase inhibitors by employing novel modifications at the reducing end of these glycomimetics. The inhibitors display a basic galactopyranosyl unit (1→4)-bonded to a 3-deoxy-4-thiopentopyranose moiety. The molecular basis of the observed inhibition has been studied by using a combination of NMR spectroscopy and molecular modeling techniques. It is demonstrated that these molecules are not recognized by Escherichia coli β-galactosidase in their ground-state conformation, with a conformational selection process taking place. In fact, the observed conformational distortion depends on the chemical nature of the compounds and results from the rotation around the glycosidic linkage (variation of φ or σ) or from the deformation of the six-membered ring of the pentopyranose. The bound conformations of the ligand are adapted in the enzymatic pocket with a variety of hydrogen-bond, van der Waals, and stacking interactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09476539_v19_n13_p4262_Calle http://hdl.handle.net/20.500.12110/paper_09476539_v19_n13_p4262_Calle |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
conformation analysis enzyme models glycosides NMR spectroscopy S ligands Conformation analysis Conformational selection Enzyme models Experimental evidence Glycosidase inhibitors Ground-state conformations Molecular modeling techniques S ligands Chemical compounds Escherichia coli Glycosides Ligands Molecular recognition Nuclear magnetic resonance spectroscopy Van der Waals forces Conformations benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D erythro pentopyranoside benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D threo pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-erythro-pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-threo-pentopyranoside beta galactosidase disaccharide ligand thioglycoside article chemical structure chemistry drug antagonism enzymology Escherichia coli nuclear magnetic resonance spectroscopy beta-Galactosidase Disaccharides Escherichia coli Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Structure Thioglucosides |
| spellingShingle |
conformation analysis enzyme models glycosides NMR spectroscopy S ligands Conformation analysis Conformational selection Enzyme models Experimental evidence Glycosidase inhibitors Ground-state conformations Molecular modeling techniques S ligands Chemical compounds Escherichia coli Glycosides Ligands Molecular recognition Nuclear magnetic resonance spectroscopy Van der Waals forces Conformations benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D erythro pentopyranoside benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D threo pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-erythro-pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-threo-pentopyranoside beta galactosidase disaccharide ligand thioglycoside article chemical structure chemistry drug antagonism enzymology Escherichia coli nuclear magnetic resonance spectroscopy beta-Galactosidase Disaccharides Escherichia coli Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Structure Thioglucosides Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| topic_facet |
conformation analysis enzyme models glycosides NMR spectroscopy S ligands Conformation analysis Conformational selection Enzyme models Experimental evidence Glycosidase inhibitors Ground-state conformations Molecular modeling techniques S ligands Chemical compounds Escherichia coli Glycosides Ligands Molecular recognition Nuclear magnetic resonance spectroscopy Van der Waals forces Conformations benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D erythro pentopyranoside benzyl 3 deoxy 4 S (beta D galactopyranosyl) 4 thio beta D threo pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-erythro-pentopyranoside benzyl-3-deoxy-4-S-(beta-D-galactopyranosyl)-4-thio-beta-D-threo-pentopyranoside beta galactosidase disaccharide ligand thioglycoside article chemical structure chemistry drug antagonism enzymology Escherichia coli nuclear magnetic resonance spectroscopy beta-Galactosidase Disaccharides Escherichia coli Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Structure Thioglucosides |
| description |
Herein, we describe the use of thioglycosides as glycosidase inhibitors by employing novel modifications at the reducing end of these glycomimetics. The inhibitors display a basic galactopyranosyl unit (1→4)-bonded to a 3-deoxy-4-thiopentopyranose moiety. The molecular basis of the observed inhibition has been studied by using a combination of NMR spectroscopy and molecular modeling techniques. It is demonstrated that these molecules are not recognized by Escherichia coli β-galactosidase in their ground-state conformation, with a conformational selection process taking place. In fact, the observed conformational distortion depends on the chemical nature of the compounds and results from the rotation around the glycosidic linkage (variation of φ or σ) or from the deformation of the six-membered ring of the pentopyranose. The bound conformations of the ligand are adapted in the enzymatic pocket with a variety of hydrogen-bond, van der Waals, and stacking interactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| title |
Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| title_short |
Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| title_full |
Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| title_fullStr |
Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| title_full_unstemmed |
Escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: Experimental evidence of conformational distortion in the molecular recognition process |
| title_sort |
escherichia coli β-galactosidase inhibitors through modifications at the aglyconic moiety: experimental evidence of conformational distortion in the molecular recognition process |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09476539_v19_n13_p4262_Calle http://hdl.handle.net/20.500.12110/paper_09476539_v19_n13_p4262_Calle |
| _version_ |
1768543142163775488 |