Targeting drug-efflux pumps - a pharmacoinformatic approach

• Authors: Karin Pleban , Dominik Kaiser , Stefan Kopp , Michael Peer , Peter Chiba , Gerhard F Ecker
• Languages of publication: EN

Abstracts

EN

In line with our studies on propafenone-type inhibitors of P-glycoprotein (P-gp), we applied several methods to approach virtual screening tools for identification of new P-gp inhibitors on one hand and the molecular basis of ligand-protein interaction on the other hand. For virtual screening, a combination of autocorrelation vectors and selforganising artificial neural networks proved extremely valuable in identifying P-gp inhibitors with structurally new scaffolds. For a closer view on the binding region for propafenone-type ligands we applied a combination of pharmacophore-driven photoaffinity labeling and protein homology modeling. On LmrA, a bacterial homologue of P-gp, we were able to identify distinct regions on transmembrane helices 3, 5 and 6 which show significant changes in the labeling pattern during different steps of the catalytic cycle.

Keywords

EN

drug-efflux pumps; photoaffinity labeling; P-glycoprotein; self-organising maps; pharmacoinformatics; propafenone

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2005
• Volume: 52
• Issue: 3
• Pages: 737-740

Dates

published

2005

received

2005-03-15

revised

2005-06-28

accepted

2005-07-18

Contributors

author

Karin Pleban

• Emerging Focus Pharmacoinformatics, Department of Medicinal Chemistry, University of Vienna, Wien, Austria

author

Dominik Kaiser

• Emerging Focus Pharmacoinformatics, Department of Medicinal Chemistry, University of Vienna, Wien, Austria

author

Stefan Kopp

• Institute of Medical Chemistry, Medical University of Vienna, Wien, Austria

author

Michael Peer

• Institute of Medical Chemistry, Medical University of Vienna, Wien, Austria

author

Peter Chiba

• Institute of Medical Chemistry, Medical University of Vienna, Wien, Austria

author

Gerhard F Ecker

• Emerging Focus Pharmacoinformatics, Department of Medicinal Chemistry, University of Vienna, Wien, Austria

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