Abstract
alpha-Amino aldehydes and bestatin are found to be effective inhibitors of a cytosolic dipeptidase (rat testicular peptidase C), and a cytosolic tripeptidase (rat kidney peptidase B, EC 3.4.11.4), as well as cytosolic leucine aminopeptidase (pig kidney peptidase S, EC 3.4.11.1). Aldehyde hydrates and bestatin share a resemblance to intermediates that might be formed during direct attack by water on peptide substrates, affording a possible explanation for their tight binding. Alternatively, inhibitors of both kinds might form derivatives of an active site nucleophile, resembling intermediates in a double-displacement mechanism. Exchange experiments with H218O suggest that bestatin is bound intact by leucine aminopeptidase, lending support to the first of these two mechanisms.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / analogs & derivatives
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Alanine / pharmacology
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Aldehydes / pharmacology*
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Aminopeptidases / antagonists & inhibitors*
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Animals
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Aspartic Acid Endopeptidases*
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Kidney / enzymology
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Kinetics
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Leucine / analogs & derivatives*
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Leucine / pharmacology
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Leucyl Aminopeptidase / antagonists & inhibitors*
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Male
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Peptide Hydrolases / isolation & purification
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Proline / analogs & derivatives
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Proline / pharmacology
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Protease Inhibitors*
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Rats
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Testis / enzymology
Substances
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Aldehydes
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Protease Inhibitors
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alaninal
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leucinal
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Proline
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Peptide Hydrolases
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peptidase C
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Aminopeptidases
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Leucyl Aminopeptidase
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tripeptide aminopeptidase
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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aspartic proteinase A
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Aspartic Acid Endopeptidases
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Leucine
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ubenimex
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prolinal
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Alanine