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S. Mabrey and J. M. Sturtevant, “Investigation of phase transitions of lipids and lipid mixtures by sensitivity differential scanning calorimetry. Proceedings of the National Academy of Sciences,” Proceedings of the National Academy of Sciences, Vol. 73, No. 11, 1976, pp. 3862-3866.

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• TITLE: Anticushing Drug Metyrapone Exhibits Specific Interactions with Serine Containing Systems. A Possible Molecular Target?

  AUTHORS: David Crouzier, Jean-Claude Debouzy, Florian Nachon, Dominique Debouzy, Guy Lallement, Frédéric Canini

  KEYWORDS: Metyrapone, Membranes, Serine, NMR, ESR, Interactions

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.2 No.4, October 18, 2011

  ABSTRACT: 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 neither 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.