Abstract
Glutamine synthetase (E.C. 6.3.1.2) – an enzyme catalyzing formation of glutamine from glutamate and ammonium ion, is one of the most important enzymes in nitrogen metabolism. Due to glutamine synthetase activity, inorganic nitrogen is incorporated in the cell metabolism and is further used in biosynthesis of several highly important metabolites. The first part of the review presents the long-dating research on inhibitors of glutamine synthetase which started with the discovery of methionine sulfoximine in 1949. Since that time several inhibitors of this enzyme, classified in the following groups: derivatives of methionine sulfoximine, phosphorus containing analogues of glutamic acid, bisphosphonates and miscellaneous inhibitors, have been developed and described. Analysis of their structure-activity relationships is presented in some detail. The second part of the paper is dedicated to potential medical application of glutamine synthetase inhibitors, which proved to act as effective anti-tuberculosis agents with high selectivity towards the pathogenic bacteria. Moreover, it was also shown that glutamine synthetase inhibitors could be successfully applied in cancer therapy.
Keywords: Glutamine Synthetase, Inhibitors, enzyme catalyzing formation, cell metabolism, structure-activity relationships, medicinal application
Mini-Reviews in Medicinal Chemistry
Title: Inhibitors of Glutamine Synthetase and their Potential Application in Medicine
Volume: 8 Issue: 9
Author(s): Lukasz Berlicki
Affiliation:
Keywords: Glutamine Synthetase, Inhibitors, enzyme catalyzing formation, cell metabolism, structure-activity relationships, medicinal application
Abstract: Glutamine synthetase (E.C. 6.3.1.2) – an enzyme catalyzing formation of glutamine from glutamate and ammonium ion, is one of the most important enzymes in nitrogen metabolism. Due to glutamine synthetase activity, inorganic nitrogen is incorporated in the cell metabolism and is further used in biosynthesis of several highly important metabolites. The first part of the review presents the long-dating research on inhibitors of glutamine synthetase which started with the discovery of methionine sulfoximine in 1949. Since that time several inhibitors of this enzyme, classified in the following groups: derivatives of methionine sulfoximine, phosphorus containing analogues of glutamic acid, bisphosphonates and miscellaneous inhibitors, have been developed and described. Analysis of their structure-activity relationships is presented in some detail. The second part of the paper is dedicated to potential medical application of glutamine synthetase inhibitors, which proved to act as effective anti-tuberculosis agents with high selectivity towards the pathogenic bacteria. Moreover, it was also shown that glutamine synthetase inhibitors could be successfully applied in cancer therapy.
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Cite this article as:
Berlicki Lukasz, Inhibitors of Glutamine Synthetase and their Potential Application in Medicine, Mini-Reviews in Medicinal Chemistry 2008; 8 (9) . https://dx.doi.org/10.2174/138955708785132800
DOI https://dx.doi.org/10.2174/138955708785132800 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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