Abstract
Calpain, a Ca2+-dependent neutral protease, is highly related to the pathogenesis of a variety of disorders and its inhibitors offer potential for therapeutic intervention. General calpain inhibitors, however, have the disadvantage of a lack of specificity or poor cellular permeability or oxidization under physiological conditions. Here, we developed a membrane-permeable specific calpain inhibitor by fusing calpastatin peptide (CS) and 11 poly-arginine peptides (11R). The 11R-fused CS (11R-CS) effectively penetrated across the plasma membrane of living neurons and significantly inhibited calpain activity in the cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium-Binding Proteins / chemical synthesis
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Calcium-Binding Proteins / pharmacokinetics*
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Calpain / antagonists & inhibitors*
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Calpain / metabolism
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Cell Death / drug effects
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Cell Death / physiology
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cell Membrane Permeability / drug effects*
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Cell Membrane Permeability / physiology
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Cells, Cultured
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Cysteine Proteinase Inhibitors / chemical synthesis
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Cysteine Proteinase Inhibitors / pharmacokinetics*
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Dose-Response Relationship, Drug
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Neurons / drug effects
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Neurons / metabolism
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Peptides / chemical synthesis
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Peptides / pharmacokinetics*
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Rats
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Substrate Specificity
Substances
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Calcium-Binding Proteins
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Cysteine Proteinase Inhibitors
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Peptides
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polyarginine
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calpastatin
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Calpain