Abstract
This study reports on the synthesis of peptides containing C-terminal acylated gem-diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl-Val-Pro-g-Val-CO-O-C(6)H(4)-NO(2) of neutrophil and pancreatic elastases that functions in a time-dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long-lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem-diamine, Cbz-Phe-g-Ala-CO-CH(2)Hal (Hal = Br, Cl).
MeSH terms
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Animals
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Cathepsin B / antagonists & inhibitors*
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Cattle
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Cysteine Proteinase Inhibitors / chemical synthesis*
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Cysteine Proteinase Inhibitors / chemistry
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Cysteine Proteinase Inhibitors / pharmacology
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Diamines / analysis
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Diamines / pharmacology
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Dipeptides / chemical synthesis
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Dipeptides / chemistry
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Dipeptides / pharmacology
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Humans
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Kinetics
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Leukocyte Elastase / antagonists & inhibitors
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Pancreatic Elastase / antagonists & inhibitors
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / chemistry
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Serine Proteinase Inhibitors / pharmacology
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Urethane / analogs & derivatives*
Substances
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Cysteine Proteinase Inhibitors
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Diamines
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Dipeptides
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Oligopeptides
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Serine Proteinase Inhibitors
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Urethane
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Pancreatic Elastase
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Leukocyte Elastase
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Cathepsin B