Abstract
Cyclic peptides have great potential as therapeutic agents and research tools but are generally impermeable to the cell membrane. Fusion of cyclic peptides with a cyclic cell-penetrating peptide produces bicyclic peptides that are cell-permeable and retain the ability to recognize specific intracellular targets. Application of this strategy to protein tyrosine phosphatase 1B and a peptidyl-prolyl cis-trans isomerase (Pin1) isomerase resulted in potent, selective, proteolytically stable, and biologically active inhibitors against the enzymes.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / pharmacology*
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Cell Line, Tumor
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Cell Membrane Permeability
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Cell-Penetrating Peptides / chemical synthesis*
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Cell-Penetrating Peptides / pharmacology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / pharmacology*
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Peptidylprolyl Isomerase / antagonists & inhibitors
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Peptidylprolyl Isomerase / chemistry
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
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Structure-Activity Relationship
Substances
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Bridged Bicyclo Compounds
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Cell-Penetrating Peptides
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Enzyme Inhibitors
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Peptides, Cyclic
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Peptidylprolyl Isomerase