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Enkephalin convertase: potent, selective, and irreversible inhibitors
Biochemical and Biophysical Research Communications
|March 29, 1983
Summary
Biproduct analogs of lysine and arginine effectively inhibit enkephalin convertase, an enzyme linked to enkephalin biosynthesis. Guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid show potent competitive inhibition.
Area of Science:
- Biochemistry
- Enzymology
- Neuroscience
Background:
- Enkephalin convertase is a carboxypeptidase B-like enzyme.
- This enzyme is physiologically associated with enkephalin biosynthesis.
Purpose of the Study:
- To identify potent inhibitors of enkephalin convertase.
- To characterize the inhibition mechanism of biproduct analogs.
Main Methods:
- Synthesis and testing of biproduct analogs of lysine and arginine.
- Enzyme kinetics to determine inhibition constants (Ki) and mechanism.
- Evaluation of irreversible inhibition using bromoacetyl-D-arginine.
Main Results:
- Guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid are potent inhibitors with Ki values of 8.8 and 7.5 nM, respectively.
- These analogs are several hundred-fold more potent against enkephalin convertase than carboxypeptidase B or N.
- Inhibition was determined to be purely competitive.
- Bromoacetyl-D-arginine demonstrated efficient irreversible inhibition.
Conclusions:
- Biproduct analogs of lysine and arginine are effective inhibitors of enkephalin convertase.
- These findings provide valuable tools for studying enkephalin biosynthesis and function.