Molecular Pharmacology and Toxicology

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Group leader: Ingebrigt Sylte


phone: +47 77644705 or +47 90834533

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Targeted inhibition of virulence factors in general is recognized as a promising approach against infectious diseases. Pathogens confronted with such compounds, will have a reduced ability to evade clearance by the human immune responses and will be hampered establishing an infection. When used as adjuvants, reduced amounts of classical, small-molecule antibiotics might be necessary to achieve efficient infection treatment.

Several human pathogenic bacteria produce and secrete toxic zinc metalloproteases, the most prominent examples being pseudolysin, aeruginolysin (both Pseudomonas aeruginosa), vibriolysin (Vibroio sp.), aureolysin (Staphylococcus aureus) and thermolysin (Leptospira). These extracellular virulence factors are central during the infection processes and are known to degrade human tissue components and components of the human immune system. We are using a combination of different molecular modelling methods (docking and scoring, ligand-based and target-based virtual screening, molecular dynamics simulations) and inhibition kinetics to study molecular mechanism and inhibition of bacterial and human zinc metalloproteinases.  Our aim is to identify selective inhibitors of the bacterial virulence factors that do not interfere with human zinc metalloproteinases.