Abstract
We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl alpha-keto-beta-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki 0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.
MeSH terms
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Aldehydes / chemistry*
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Cathepsin B / antagonists & inhibitors*
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Cathepsin B / metabolism
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Cathepsin L
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Cathepsins / antagonists & inhibitors*
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Cathepsins / metabolism
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Cysteine Endopeptidases
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Cysteine Proteinase Inhibitors / chemistry
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Cysteine Proteinase Inhibitors / metabolism
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Cysteine Proteinase Inhibitors / pharmacology*
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Endopeptidases*
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Humans
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Peptides / chemistry*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Substrate Specificity
Substances
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Aldehydes
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Cysteine Proteinase Inhibitors
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Peptides
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Recombinant Proteins
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Cathepsins
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Endopeptidases
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Cysteine Endopeptidases
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Cathepsin B
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CTSL protein, human
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Cathepsin L