Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus
Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1493474 |
| _version_ | 1818503136157892608 |
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| author | Jure Borišek Sara Pintar Mitja Ogrizek Simona Golič Grdadolnik Vesna Hodnik Dušan Turk Andrej Perdih Marjana Novič |
| author_facet | Jure Borišek Sara Pintar Mitja Ogrizek Simona Golič Grdadolnik Vesna Hodnik Dušan Turk Andrej Perdih Marjana Novič |
| author_sort | Jure Borišek |
| collection | DOAJ |
| description | Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target. |
| first_indexed | 2024-12-10T21:19:57Z |
| format | Article |
| id | doaj.art-183744445d2b4e33acfeefddb1bf33c9 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-10T21:19:57Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-183744445d2b4e33acfeefddb1bf33c92022-12-22T01:33:10ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-013311239124710.1080/14756366.2018.14934741493474Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureusJure Borišek0Sara Pintar1Mitja Ogrizek2Simona Golič Grdadolnik3Vesna Hodnik4Dušan Turk5Andrej Perdih6Marjana Novič7National Institute of ChemistryJozef Stefan InstituteNational Institute of ChemistryNational Institute of ChemistryInfrastructural Center for Surface Plasmon ResonanceJozef Stefan InstituteNational Institute of ChemistryNational Institute of ChemistryAutolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target.http://dx.doi.org/10.1080/14756366.2018.1493474Autolysin Eglycoside hydrolasevirtual screeningSPRSTD NMR |
| spellingShingle | Jure Borišek Sara Pintar Mitja Ogrizek Simona Golič Grdadolnik Vesna Hodnik Dušan Turk Andrej Perdih Marjana Novič Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus Journal of Enzyme Inhibition and Medicinal Chemistry Autolysin E glycoside hydrolase virtual screening SPR STD NMR |
| title | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
| title_full | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
| title_fullStr | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
| title_full_unstemmed | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
| title_short | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
| title_sort | discovery of phenylureido piperidinyl benzamides as prospective inhibitors of bacterial autolysin e from staphylococcus aureus |
| topic | Autolysin E glycoside hydrolase virtual screening SPR STD NMR |
| url | http://dx.doi.org/10.1080/14756366.2018.1493474 |
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