Metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone) is a drug largely used as inhibitor of glucocorticoid synthesis. Although its binding to various proteins has been well indentified, its accurate molecular mechanism of action remains unknown. Therefore, the interactions of metyrapone (MET) with various membrane components such as phospholipids, cholesterol, their corresponding polar heads and a model serine containing peptide have been investigated by NMR and ESR methods. It was found that

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... her cholesterol nor most of the phospholipids tested, nor dimyristin exhibit any interaction with MET, except phosphatidylserine (DMPS). Furthermore, only serine bearing polar head (O-phosphoserine) showed an association with MET (stoechiometry 1:1, Kd = 3200M-1). As similar observations were also performed on serine alone and in the presence of the serine containing model peptide, (NASDSDGQDL), a possible implication of these interactions in the binding recognition of MET on serine-containing active site was finally tested and discussed. Interactions with the Model Peptide NASDSDGQDL After purity control and attribution of peptide protons using classical NMR methods [50], the same method as before was used on equimolar mixtures of MET/peptide. By comparison with the spectrum of pure MET (Figure 4(a) ) significant chemical shift variations were observed on the MET/peptide sample, as shown on Figure 4(a) , similar as with OPS/MET reparations. Moreover, the p