Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>...

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Autores principales:	Martin Löwer, Tim Geppert, Petra Schneider, Benjamin Hoy, Silja Wessler, Gisbert Schneider
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d55323295b44fc4a0f7665cde6b9ee5
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spelling	oai:doaj.org-article:5d55323295b44fc4a0f7665cde6b9ee52021-11-18T06:56:24ZInhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.1932-620310.1371/journal.pone.0017986https://doaj.org/article/5d55323295b44fc4a0f7665cde6b9ee52011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483848/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>This study demonstrates that receptor-based virtual screening with a permissive ('fuzzy') pharmacophore model can help identify small bioactive agents for combating bacterial infection.Martin LöwerTim GeppertPetra SchneiderBenjamin HoySilja WesslerGisbert SchneiderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17986 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martin Löwer Tim Geppert Petra Schneider Benjamin Hoy Silja Wessler Gisbert Schneider Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>This study demonstrates that receptor-based virtual screening with a permissive ('fuzzy') pharmacophore model can help identify small bioactive agents for combating bacterial infection.
format	article
author	Martin Löwer Tim Geppert Petra Schneider Benjamin Hoy Silja Wessler Gisbert Schneider
author_facet	Martin Löwer Tim Geppert Petra Schneider Benjamin Hoy Silja Wessler Gisbert Schneider
author_sort	Martin Löwer
title	Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
title_short	Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
title_full	Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
title_fullStr	Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
title_full_unstemmed	Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
title_sort	inhibitors of helicobacter pylori protease htra found by 'virtual ligand' screening combat bacterial invasion of epithelia.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/5d55323295b44fc4a0f7665cde6b9ee5
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Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.

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