Research article - Peer-reviewed, 2008
Evaluation of the amino acid binding site of Mycobacterium tuberculosis glutamine synthetase for drug discoveryNordqvist, Anneli; Nilsson, Mikael T.; Rottger, Svenja; Odell, Luke R.; Krajewski, Wojciech W.; Andersson, C. Evalena; Larhed, Mats; Mowbray, Sherry L.; Karlen, Anders
AbstractA combination of a literature survey, structure-based virtual screening and synthesis of a small library was performed to identify hits to the potential antimycobacterial drug target, glutamine synthetase. The best inhibitor identified from the literature survey was (2S, 5R)-2,6-diamino-5-hydroxyhexanoic acid ( 4, IC(50) of 610 +/- 15 mu M). In the virtual screening 46,400 compounds were docked and subjected to a pharmacophore search. Of these compounds, 29 were purchased and tested in a biological assay, allowing three novel inhibitors containing an aromatic scaffold to be identified. Based on one of the hits from the virtual screening a small library of 15 analogues was synthesized producing four compounds that inhibited glutamine synthetase. (C) 2008 Elsevier Ltd. All rights reserved.
Keywordsvirtual screening; glutamine synthetase; gamma-glutamyl : ammonia ligase
Published inBioorganic and Medicinal Chemistry
2008, volume: 16, number: 10, pages: 5501-5513
Nilsson, Mikael T.
Odell, Luke R.
Krajewski, Wojciech W.
Andersson, C. Evalena
Swedish University of Agricultural Sciences, Department of Molecular Biology
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SDG3 Good health and well-being
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