Abstract
The emergence and spread of multidrug-resistant pathogens are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of "reverse" thia analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an α-substituted fosmidomycin derivative.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldose-Ketose Isomerases / antagonists & inhibitors*
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Aldose-Ketose Isomerases / genetics
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Aldose-Ketose Isomerases / metabolism
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Amino Acid Sequence
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Anti-Infective Agents / chemical synthesis
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / pharmacology*
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Crystallography, X-Ray
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Drug Discovery / methods*
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Fosfomycin / analogs & derivatives*
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Fosfomycin / chemical synthesis
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Fosfomycin / chemistry
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Fosfomycin / pharmacology
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Models, Chemical
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / genetics
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / enzymology
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Plasmodium falciparum / genetics
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Protein Binding
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Protein Structure, Tertiary
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Protozoan Proteins / antagonists & inhibitors
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Protozoan Proteins / genetics
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Protozoan Proteins / metabolism
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Sequence Homology, Amino Acid
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Stereoisomerism
Substances
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Anti-Infective Agents
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Bacterial Proteins
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Protozoan Proteins
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Fosfomycin
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fosmidomycin
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1-deoxy-D-xylulose 5-phosphate reductoisomerase
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Aldose-Ketose Isomerases