Abstract |
The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.
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Authors | Komagal Kannan Sivaraman, Alessandro Paiardini, Marcin Sieńczyk, Chiara Ruggeri, Christine A Oellig, John P Dalton, Peter J Scammells, Marcin Drag, Sheena McGowan |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 56
Issue 12
Pg. 5213-7
(Jun 27 2013)
ISSN: 1520-4804 [Electronic] United States |
PMID | 23713488
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Phosphorous Acids
- phosphonic acid
- Arginine
- CD13 Antigens
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Topics |
- Arginine
(chemistry)
- Biomimetic Materials
(chemical synthesis, chemistry, pharmacology)
- CD13 Antigens
(antagonists & inhibitors, chemistry)
- Catalytic Domain
- Chemistry Techniques, Synthetic
- Enzyme Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Models, Molecular
- Phosphorous Acids
(chemistry)
- Plasmodium falciparum
(enzymology)
- Structure-Activity Relationship
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