Abstract
Tripeptidyl peptidase II is an intracellular exopeptidase, which has been purified from rat liver and human erythrocytes. An efficient specific inhibitor was obtained through beta-elimination of phosphate from the phosphopeptide Arg-Ala-Ser(P)-Val-Ala. The dehydroalanine-containing peptide formed was a competitive inhibitor with a Ki of 0.02 +/- 0.01 microM. This study demonstrated that replacing a serine residue in a good inhibitor with a dehydroalanine residue reduced the Ki 45 times. It is proposed that dehydroalanine-containing peptides could be of interest in the development of inhibitors for other peptidases as well.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / analogs & derivatives*
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Amino Acid Sequence
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Aminopeptidases
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Animals
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Erythrocytes / enzymology
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Kinetics
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Liver / enzymology
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Magnetic Resonance Spectroscopy
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Molecular Sequence Data
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Phosphopeptides / chemical synthesis
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Phosphopeptides / chemistry
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Phosphopeptides / pharmacology*
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Protease Inhibitors / pharmacology*
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Rats
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Serine Endopeptidases / blood
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Serine Endopeptidases / metabolism*
Substances
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Oligopeptides
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Phosphopeptides
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Protease Inhibitors
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dehydroalanine
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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tripeptidyl-peptidase 2
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Serine Endopeptidases
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Alanine