Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand' Screening Combat Bacterial Invasion of Epithelia
| LEADER | naa a22 4500 | ||
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| 001 | 528782150 | ||
| 005 | 20180924065513.0 | ||
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| 008 | 180924e20110331xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000034833 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0017986 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/34833 | ||
| 245 | 0 | 0 | |a Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand' Screening Combat Bacterial Invasion of Epithelia |h [Elektronische Daten] |c [Martin Löwer, Tim Geppert, Petra Schneider, Benjamin Hoy, Silja Wessler, Gisbert Schneider] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a Background The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand') for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy') pharmacophore model can help identify small bioactive agents for combating bacterial infection. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Löwer |D Martin |e joint author | |
| 700 | 1 | |a Geppert |D Tim |e joint author | |
| 700 | 1 | |a Schneider |D Petra |e joint author | |
| 700 | 1 | |a Hoy |D Benjamin |e joint author | |
| 700 | 1 | |a Wessler |D Silja |e joint author | |
| 700 | 1 | |a Schneider |D Gisbert |e joint author | |
| 773 | 0 | |t PLoS ONE |d Lawrence, Kan. : Public Library of Science |g 6 (3), p. e17986 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/34833 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/34833 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Löwer |D Martin |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Geppert |D Tim |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schneider |D Petra |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hoy |D Benjamin |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Wessler |D Silja |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schneider |D Gisbert |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d Lawrence, Kan. : Public Library of Science |g 6 (3), p. e17986 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||