Go to page
 

Bibliographic Metadata

Title
Inhibitors of Helicobacter pylori protease HtrA found by 'Virtual Ligand' screening combat bacterial invasion of epithelia / Martin Löwer, Tim Geppert, Petra Schneider, Benjamin Hoy, Silja Wessler, Gisbert Schneider
AuthorLöwer, Martin In der Gemeinsamen Normdatei der DNB nachschlagen ; Geppert, Tim ; Schneider, Petra ; Hoy, Benjamin ; Wessler, Silja ; Schneider, Gisbert In der Gemeinsamen Normdatei der DNB nachschlagen
Published in
PLoS One, 2011,
Published2011
DescriptionIllustrationen
LanguageEnglish
Document typeJournal Article
Keywords (DE)Heliobacter pylori
URNurn:nbn:at:at-ubs:3-29 Persistent Identifier (URN)
DOI10.1371/journal.pone.0017986 
Restriction-Information
 The work is publicly available
Files
Inhibitors of Helicobacter pylori protease HtrA found by 'Virtual Ligand' screening combat bacterial invasion of epithelia [0.34 mb]
Links
Reference
Classification
Abstract (English)

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.