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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Binding, Competitive
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Cell Line, Tumor
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Dipeptides / chemical synthesis*
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Dipeptides / chemistry
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Dipeptides / pharmacology
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Fluorescence Resonance Energy Transfer
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Humans
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Molecular
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / chemistry*
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Peptidylprolyl Isomerase / isolation & purification
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Peptidylprolyl Isomerase / metabolism
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Phosphopeptides / chemistry*
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Phosphopeptides / metabolism
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Phosphoproteins / chemical synthesis*
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Phosphoproteins / chemistry
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Phosphoproteins / pharmacology
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Protein Structure, Tertiary
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Dipeptides
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Ligands
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NIMA-Interacting Peptidylprolyl Isomerase
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Phosphopeptides
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Phosphoproteins
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Recombinant Proteins
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acetyl-phosphothreonyl-prolinamide
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PIN1 protein, human
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Peptidylprolyl Isomerase