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Research article - Peer-reviewed, 2008

Evaluation of the amino acid binding site of Mycobacterium tuberculosis glutamine synthetase for drug discovery

Nordqvist, Anneli; Nilsson, Mikael T.; Rottger, Svenja; Odell, Luke R.; Krajewski, Wojciech W.; Andersson, C. Evalena; Larhed, Mats; Mowbray, Sherry L.; Karlen, Anders


A 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.


virtual screening; glutamine synthetase; gamma-glutamyl : ammonia ligase

Published in

Bioorganic and Medicinal Chemistry
2008, volume: 16, number: 10, pages: 5501-5513

Authors' information

Nordqvist, Anneli
Uppsala University
Nilsson, Mikael T.
Uppsala University
Röttger, Svenja
Uppsala University
Odell, Luke R.
Uppsala University
Krajewski, Wojciech W.
Uppsala University
Andersson, C. Evalena
Uppsala University
Larhed, Mats
Uppsala University
Mowbray, Sherry
Swedish University of Agricultural Sciences, Department of Molecular Biology
Karlén, Anders
Uppsala University

Sustainable Development Goals

SDG3 Good health and well-being

UKÄ Subject classification

Food Science

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