Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes

Toshihiko Takeuchi; Arnd Böttcher; Cindy M. Quezada; Thomas J. Meade; Harry B. Gray

doi:10.1016/S0968-0896(98)00272-7

Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes

Toshihiko Takeuchi, Arnd Böttcher, Cindy M. Quezada, Thomas J. Meade^*, Harry B. Gray

^*Corresponding author for this work

Chemistry

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

98 Scopus citations

Abstract

Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH₃)₂]⁺ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human α-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex. Copyright (C) 1999 Elsevier Science Ltd.

Original language	English (US)
Pages (from-to)	815-819
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	7
Issue number	5
DOIs	https://doi.org/10.1016/S0968-0896(98)00272-7
State	Published - May 1999

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0968-0896(98)00272-7

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title = "Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes",

abstract = "Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH3)2]+ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human α-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex. Copyright (C) 1999 Elsevier Science Ltd.",

author = "Toshihiko Takeuchi and Arnd B{\"o}ttcher and Quezada, {Cindy M.} and Meade, {Thomas J.} and Gray, {Harry B.}",

note = "Funding Information: A. B. thanks the Alexander von Humboldt foundation for a postdoctoral fellowship. This work was supported by NSF and Redox Pharmaceutical Corporation.",

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T1 - Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes

AU - Takeuchi, Toshihiko

AU - Böttcher, Arnd

AU - Quezada, Cindy M.

AU - Meade, Thomas J.

AU - Gray, Harry B.

N1 - Funding Information: A. B. thanks the Alexander von Humboldt foundation for a postdoctoral fellowship. This work was supported by NSF and Redox Pharmaceutical Corporation.

PY - 1999/5

Y1 - 1999/5

N2 - Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH3)2]+ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human α-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex. Copyright (C) 1999 Elsevier Science Ltd.

AB - Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH3)2]+ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human α-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex. Copyright (C) 1999 Elsevier Science Ltd.

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Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes

Abstract

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