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钴(III)席夫碱配合物对嗜热菌蛋白酶和人α-凝血酶的抑制作用。

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

作者信息

Takeuchi T, Böttcher A, Quezada C M, Meade T J, Gray H B

机构信息

Division of Biology and the Beckman Institute, California Institute of Technology, Pasadena 91125, USA.

出版信息

Bioorg Med Chem. 1999 May;7(5):815-9. doi: 10.1016/s0968-0896(98)00272-7.

DOI:10.1016/s0968-0896(98)00272-7
PMID:10400334
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 alpha-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.

摘要

钴(III)席夫碱配合物已被证明能抑制眼部疱疹病毒的复制。众所周知,这些配合物对含氮供体如组氨酸残基具有高亲和力,并且它们有可能与对病毒复制至关重要的一种酶结合(并抑制其活性)。在模型研究中,我们发现[Co(acacen)(NH3)2]+在毫摩尔浓度下是嗜热菌蛋白酶的一种有效的不可逆抑制剂;它也能抑制人α-凝血酶。与活性位点组氨酸进行轴向配体交换是推测的抑制机制。在加入钴(III)配合物之前,通过将一种可逆抑制剂结合到活性位点,可以保护嗜热菌蛋白酶和凝血酶的活性。

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