dc.contributor.author |
Manos-Turvey, A |
en |
dc.contributor.author |
Cergol, KM |
en |
dc.contributor.author |
Salam, NK |
en |
dc.contributor.author |
Bulloch, Esther |
en |
dc.contributor.author |
Chi, G |
en |
dc.contributor.author |
Pang, A |
en |
dc.contributor.author |
Britton, WJ |
en |
dc.contributor.author |
West, NP |
en |
dc.contributor.author |
Baker, Edward |
en |
dc.contributor.author |
Lott, Jeremy |
en |
dc.contributor.author |
Payne, RJ |
en |
dc.date.accessioned |
2013-04-03T22:45:45Z |
en |
dc.date.issued |
2012-12-14 |
en |
dc.identifier.citation |
Organic and Biomolecular Chemistry 10(46):9223-9236 14 Dec 2012 |
en |
dc.identifier.issn |
1477-0520 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/20353 |
en |
dc.description.abstract |
Mycobacterium tuberculosis salicylate synthase (MbtI) catalyses the first committed step in the biosynthesis of mycobactin T, an iron-chelating siderophore essential for the virulence and survival of M. tuberculosis. Co-crystal structures of MbtI with members of a first generation inhibitor library revealed large inhibitor-induced rearrangements within the active site of the enzyme. This plasticity of the MbtI active site was probed via the preparation of a library of inhibitors based on a 2,3-dihydroxybenzoate scaffold with a range of substituted phenylacrylate side chains appended to the C3 position. Most compounds exhibited moderate inhibitory activity against the enzyme, with inhibition constants in the micromolar range, while several dimethyl ester variants possessed promising anti-tubercular activity in vitro. © 2012 The Royal Society of Chemistry. |
en |
dc.relation.ispartofseries |
Organic and Biomolecular Chemistry |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1477-0520/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1039/c2ob26736e |
en |
pubs.issue |
46 |
en |
pubs.begin-page |
9223 |
en |
pubs.volume |
10 |
en |
dc.identifier.pmid |
23108268 |
en |
pubs.end-page |
9236 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
364529 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2013-04-04 |
en |
pubs.dimensions-id |
23108268 |
en |