Abstract
We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bacterial Outer Membrane Proteins / antagonists & inhibitors*
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Bacterial Outer Membrane Proteins / chemistry
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Bacterial Outer Membrane Proteins / metabolism
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Binding Sites
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Structure
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Protein Binding
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Protein Structure, Tertiary
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / metabolism
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Structure-Activity Relationship
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Yersinia / enzymology*
Substances
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Bacterial Outer Membrane Proteins
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Enzyme Inhibitors
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Oligopeptides
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PTPN1 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases
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yopH protein, Yersinia