Document Report Card

ID: ALA1140329

Journal: J Med Chem

Title: Control of protein-protein interactions: structure-based discovery of low molecular weight inhibitors of the interactions between Pin1 WW domain and phosphopeptides.

Authors: Smet C, Duckert JF, Wieruszeski JM, Landrieu I, Buée L, Lippens G, Déprez B.

Abstract: Interactions involving phosphorylated Ser/Thr-Pro motifs in proteins play a key role in numerous regulatory processes in the cell. Here, we investigate potential ligands of the WW binding domain of Pin1 in order to inhibit protein-protein interactions between Pin1 and phosphopeptides. Our structure-based strategy implies the synthesis of analogues of the Ac-Thr(PO(3)H(2))-Pro-NH(2) dipeptide and relies on high resolution NMR spectroscopy to accurately measure the affinity constants even in the high micromolar range.

CiteXplore: 16033261

DOI: 10.1021/jm0500119