Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids

S. Wilk; L. S. Thurston

doi:10.1016/0143-4179(90)90129-M

Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids

S. Wilk, L. S. Thurston

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC 3.4.11.7). Thiol derivatives of glutamate and aspartate in which the α-COOH group was replaced by -CH₂SH were synthesized as inhibitors of glutamyl aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase (K_i = 4 × 10^-7M) but even more potently inhibited microsomal alanyl aminopeptidase (K_i = 2.5 × 10^-7M). Aspartate thiol (β-homocysteine) was a less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl aminopeptidase: K_i = 1.2 × 10^-6M; microsomal alanyl aminopeptidase: K_i = 7.5 × 10^-6M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate thiol blocked the conversion of angiotensin II to angiotensin III. These derivatives are more selective than amastatin and may be of value in studies probing the biological significance of angiotensin III.

Original language	English
Pages (from-to)	163-168
Number of pages	6
Journal	Neuropeptides
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/0143-4179(90)90129-M
State	Published - Jul 1990
Externally published	Yes

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title = "Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids",

abstract = "Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC 3.4.11.7). Thiol derivatives of glutamate and aspartate in which the α-COOH group was replaced by -CH2SH were synthesized as inhibitors of glutamyl aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase (Ki = 4 × 10-7M) but even more potently inhibited microsomal alanyl aminopeptidase (Ki = 2.5 × 10-7M). Aspartate thiol (β-homocysteine) was a less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl aminopeptidase: Ki = 1.2 × 10-6M; microsomal alanyl aminopeptidase: Ki = 7.5 × 10-6M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate thiol blocked the conversion of angiotensin II to angiotensin III. These derivatives are more selective than amastatin and may be of value in studies probing the biological significance of angiotensin III.",

author = "S. Wilk and Thurston, {L. S.}",

note = "Funding Information: Supported by NS-17392,a Research Scientist Award MH-00350to S.W. and a trainingg rantS T3DA-07135to L.S.T.",

year = "1990",

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doi = "10.1016/0143-4179(90)90129-M",

language = "English",

volume = "16",

pages = "163--168",

journal = "Neuropeptides",

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T1 - Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids

AU - Wilk, S.

AU - Thurston, L. S.

N1 - Funding Information: Supported by NS-17392,a Research Scientist Award MH-00350to S.W. and a trainingg rantS T3DA-07135to L.S.T.

PY - 1990/7

Y1 - 1990/7

N2 - Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC 3.4.11.7). Thiol derivatives of glutamate and aspartate in which the α-COOH group was replaced by -CH2SH were synthesized as inhibitors of glutamyl aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase (Ki = 4 × 10-7M) but even more potently inhibited microsomal alanyl aminopeptidase (Ki = 2.5 × 10-7M). Aspartate thiol (β-homocysteine) was a less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl aminopeptidase: Ki = 1.2 × 10-6M; microsomal alanyl aminopeptidase: Ki = 7.5 × 10-6M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate thiol blocked the conversion of angiotensin II to angiotensin III. These derivatives are more selective than amastatin and may be of value in studies probing the biological significance of angiotensin III.

AB - Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC 3.4.11.7). Thiol derivatives of glutamate and aspartate in which the α-COOH group was replaced by -CH2SH were synthesized as inhibitors of glutamyl aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase (Ki = 4 × 10-7M) but even more potently inhibited microsomal alanyl aminopeptidase (Ki = 2.5 × 10-7M). Aspartate thiol (β-homocysteine) was a less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl aminopeptidase: Ki = 1.2 × 10-6M; microsomal alanyl aminopeptidase: Ki = 7.5 × 10-6M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate thiol blocked the conversion of angiotensin II to angiotensin III. These derivatives are more selective than amastatin and may be of value in studies probing the biological significance of angiotensin III.

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DO - 10.1016/0143-4179(90)90129-M

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JO - Neuropeptides

JF - Neuropeptides

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ER -

Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids

Abstract

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