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DXR Inhibition by P...
DXR Inhibition by Potent Mono- and Disubstituted Fosmidomycin Analogues
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- Jansson, Anna, 1979- (author)
- Uppsala universitet,Struktur- och molekylärbiologi,T. Alwyn Jones, Sherry L. Mowbray
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- Więckowska, Anna (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Anders Karlèn, Mats Larhed
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- Björkelid, Christofer (author)
- Uppsala universitet,Struktur- och molekylärbiologi,T. Alwyn Jones, Sherry L. Mowbray
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- Yahiaoui, Samir (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Anders Karlèn, Mats Larhed
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- Sooriyaarachchi, Sanjeewani (author)
- Uppsala universitet,Struktur- och molekylärbiologi,T. Alwyn Jones, Sherry L. Mowbray
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- Lindh, Martin (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Anders Karlèn, Mats Larhed
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- Bergfors, Terese (author)
- Uppsala universitet,Struktur- och molekylärbiologi,T. Alwyn Jones, Sherry L. Mowbray
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- Dharavath, Shyamraj (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Anders Karlèn, Mats Larhed
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- Desroses, Matthieu (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Anders Karlèn, Mats Larhed
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- Suresh, Surisetti (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Anders Karlèn, Mats Larhed
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- Andaloussi, Mounir (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Anders Karlèn, Mats Larhed
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- Nikhil, Rautela (author)
- AstraZeneca India Private Limited
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- Sreevalli, Sharma (author)
- AstraZeneca India Private Limited
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- Srinivasa, Bachally R. (author)
- AstraZeneca India Private Limited
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- Larhed, Mats (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Jones, T. Alwyn (author)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Karlén, Anders (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Mowbray, Sherry L. (author)
- Uppsala universitet,Struktur- och molekylärbiologi
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(creator_code:org_t)
- 2013-07-17
- 2013
- English.
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:15, s. 6190-6199
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https://uu.diva-port... (primary) (Raw object)
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http://uu.diva-porta...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- The antimalarial compound fosmidomycin targets DXR, the enzyme that catalyzes the first committed step in the MEP pathway producing the universally essential isoprenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. The MEP pathway is used by a number of pathogens, including Mycobacterium tuberculosis and apicomplexan parasites, and differs from the classical mevalonate pathway that is essential in humans. Using a structure-based approach, we designed a number of analogues of fosmidomycin, including a series that are substituted in both the Cα and the hydroxamate positions. The latter proved to be a stable framework for the design of inhibitors that extend from the cramped substrate-binding site and can, for the first time, bridge the substrate and cofactor binding sites. A number of these compounds are more potent than fosmidomycin in terms of killing Plasmodium falciparum in an in vitro assay; the best has an IC50 of 40 nM.
Subject headings
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Keyword
- Mycobacterium tuberculosis
- 1-deoxy-D-xylulose 5-phosphate reductoisomerase
- DXR
- Biologi med inriktning mot strukturbiologi
- Biology with specialization in Structural Biology
- Medicinal Chemistry
- Läkemedelskemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Jansson, Anna, 1 ...
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Więckowska, Anna
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Björkelid, Chris ...
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Yahiaoui, Samir
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Sooriyaarachchi, ...
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Lindh, Martin
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show more...
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Bergfors, Terese
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Dharavath, Shyam ...
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Desroses, Matthi ...
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Suresh, Surisett ...
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Andaloussi, Moun ...
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Nikhil, Rautela
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Sreevalli, Sharm ...
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Srinivasa, Bacha ...
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Larhed, Mats
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Jones, T. Alwyn
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Karlén, Anders
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Mowbray, Sherry ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
- Articles in the publication
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Journal of Medic ...
- By the university
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Uppsala University