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Carola Tilgmann, Piero Pollesello, Martti Ovaska, Juha Kaivola, Jarmo Pystynen, Eija Tiainen, Marjo Yliperttula, Arto Annila and Jouko Levijoki Discovery and Structural Characterization of a Phospholamban-Binding Cyclic Peptide and Design of Novel Inhibitors of Phospholamban Chemical Biology & Drug Design 81

Article first published online: 6 JUN 2012 | DOI: 10.1111/j.1747-0285.2012.01409.x

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Molecules able to interfere with the inhibitory activity of phospholamban (PLB) on SERCA2a were discovered. PLB was used as target for a phage display peptide library screening. The cyclic peptide C-Y-W-E-L-EW-L-P-C-A was found to bind to PLB and interfere with its activity. Its structure was determined and a model of this interaction with PLB was built. A pharmacophore was defined and used for the design of small molecules. Examples of such molecules were synthesized and characterized as phospholamban inhibitors.

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