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

Takeuchi, Toshihiko and Böttcher, Arnd and Quezada, Cindy M. and Meade, Thomas J. and Gray, Harry B. (1999) Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes. Bioorganic and Medicinal Chemistry, 7 (5). pp. 815-819. ISSN 0968-0896. doi:10.1016/S0968-0896(98)00272-7.

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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)(NH_3)_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.

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Gray, Harry B.0000-0002-7937-7876
Additional Information:© 1999 Elsevier Science Ltd. Received 25 August 1998, Accepted 21 October 1998, Available online 28 May 1999. 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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Alexander von Humboldt FoundationUNSPECIFIED
Redox Pharmaceutical CorporationUNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20170808-111051171
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Official Citation:Toshihiko Takeuchi, Arnd Böttcher, Cindy M. Quezada, Thomas J. Meade, Harry B. Gray, Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes, Bioorganic & Medicinal Chemistry, Volume 7, Issue 5, May 1999, Pages 815-819, ISSN 0968-0896, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79933
Deposited By: Tony Diaz
Deposited On:09 Aug 2017 19:07
Last Modified:15 Nov 2021 17:51

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