Enkephalin convertase: Potent, selective, and irreversible inhibitors

Lloyd D. Fricker; Thomas H. Plummer; Solomon H. Snyder

doi:10.1016/0006-291X(83)91398-0

Enkephalin convertase: Potent, selective, and irreversible inhibitors

Lloyd D. Fricker, Thomas H. Plummer, Solomon H. Snyder

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63 Scopus citations

Abstract

Biproduct analogs of lysine and arginine are potent inhibitors of enkephalin convertase, a carboxypeptidase B-like enzyme which appears to be physiologically associated with enkephalin biosynthesis. The most effective derivatives are guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid with respective K_i's of 8.8 and 7.5 nM. These dicarboxylic acid analogs of arginine are several hundred fold more potent towards enkephalin convertase than towards carboxypeptidase B or N. Kinetic analysis indicates the pure competitive nature of the inhibition. Bromoacetyl-D-arginine, an irreversible inhibitor of carboxypeptidase B and N, is also an efficient irreversible inhibitor of enkephalin convertase.

Original language	English (US)
Pages (from-to)	994-1000
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	111
Issue number	3
DOIs	https://doi.org/10.1016/0006-291X(83)91398-0
State	Published - Mar 29 1983
Externally published	Yes

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "Enkephalin convertase: Potent, selective, and irreversible inhibitors",

abstract = "Biproduct analogs of lysine and arginine are potent inhibitors of enkephalin convertase, a carboxypeptidase B-like enzyme which appears to be physiologically associated with enkephalin biosynthesis. The most effective derivatives are guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid with respective Ki's of 8.8 and 7.5 nM. These dicarboxylic acid analogs of arginine are several hundred fold more potent towards enkephalin convertase than towards carboxypeptidase B or N. Kinetic analysis indicates the pure competitive nature of the inhibition. Bromoacetyl-D-arginine, an irreversible inhibitor of carboxypeptidase B and N, is also an efficient irreversible inhibitor of enkephalin convertase.",

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T1 - Enkephalin convertase

T2 - Potent, selective, and irreversible inhibitors

AU - Fricker, Lloyd D.

AU - Plummer, Thomas H.

AU - Snyder, Solomon H.

N1 - Funding Information: Supported Training grant

PY - 1983/3/29

Y1 - 1983/3/29

N2 - Biproduct analogs of lysine and arginine are potent inhibitors of enkephalin convertase, a carboxypeptidase B-like enzyme which appears to be physiologically associated with enkephalin biosynthesis. The most effective derivatives are guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid with respective Ki's of 8.8 and 7.5 nM. These dicarboxylic acid analogs of arginine are several hundred fold more potent towards enkephalin convertase than towards carboxypeptidase B or N. Kinetic analysis indicates the pure competitive nature of the inhibition. Bromoacetyl-D-arginine, an irreversible inhibitor of carboxypeptidase B and N, is also an efficient irreversible inhibitor of enkephalin convertase.

AB - Biproduct analogs of lysine and arginine are potent inhibitors of enkephalin convertase, a carboxypeptidase B-like enzyme which appears to be physiologically associated with enkephalin biosynthesis. The most effective derivatives are guanidinoethylmercaptosuccinic acid and guanidinopropylsuccinic acid with respective Ki's of 8.8 and 7.5 nM. These dicarboxylic acid analogs of arginine are several hundred fold more potent towards enkephalin convertase than towards carboxypeptidase B or N. Kinetic analysis indicates the pure competitive nature of the inhibition. Bromoacetyl-D-arginine, an irreversible inhibitor of carboxypeptidase B and N, is also an efficient irreversible inhibitor of enkephalin convertase.

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Enkephalin convertase: Potent, selective, and irreversible inhibitors

Abstract

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