Inhibiting protein-membrane interactions: towards new therapeutic strategies

The goal of the present proposal is to find compounds able to hinder the binding of Proteinase 3 to the neutrophil plasma membrane in vitro. Proteinase 3 is a neutrophil enzyme, present at the surface of the neutrophil plasma membrane and which has been i dentified as a drug target for a number of inflammatory diseases and possibly leukaemia. We have studied many salient features of Proteinase 3 for many years and we recently unravelled its membrane binding mechanism using a combination of theoretical and experimental approaches. We are thus in a world-leading position to successfully develop inhibitors of Proteinase 3 membrane binding. We will use a combination of in silico and in vitro approaches, and the success of the project highly depends on the coll aboration between the French (Cochin hospital, Paris) and Norwegian (UiB) groups.