Targeting drug-efflux pumps - a pharmacoinformatic approach

• Autorzy: Pleban K. , Kaiser D. , Kopp S. , Peer M. , Chiba P. , Ecker G.F.
• Języki publikacji: EN

Abstrakty

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.

Słowa kluczowe

EN

transmembrane; P-glycoprotein; ligand-protein interaction; self-organising map; propafenone; drug-efflux pump

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2005
• Tom: 52
• Numer: 3
• Opis fizyczny: p.737-740,fig.,ref.

Twórcy

autor

Pleban K.

• University of Vienna, Vienna, Austria

autor

Kaiser D.

autor

Kopp S.

autor

Peer M.

autor

Chiba P.

autor

Ecker G.F.

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