Abstract
Desferri-exochelins are siderophores secreted by Mycobacterium tuberculosis that are both lipid- and water-soluble and have a high binding affinity for iron. Desferri-exochelin 772SM inhibits DNA replication and ribonucleotide reductase activity at 10-fold less concentration than the lipid-insoluble iron chelator deferoxamine, which is currently in clinical use. Neither chelator can extract iron directly from ribonucleotide reductase. However, because of its lipid-solubility and high binding affinity, desferri-exochelin is able to enter cells rapidly and access intracellular iron, while deferoxamine has limited capacity to cross the cell membrane.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Breast Neoplasms / enzymology
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Breast Neoplasms / metabolism
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Cell Line, Tumor
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DNA / antagonists & inhibitors
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DNA / biosynthesis
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DNA Replication / drug effects
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Deferoxamine / pharmacology
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Electron Spin Resonance Spectroscopy
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Free Radicals / metabolism
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Humans
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Hydrophobic and Hydrophilic Interactions
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Iron Chelating Agents / chemistry*
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Iron Chelating Agents / pharmacokinetics
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Iron Chelating Agents / pharmacology*
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Peptides, Cyclic / chemistry*
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Peptides, Cyclic / pharmacokinetics
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Peptides, Cyclic / pharmacology*
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Ribonucleotide Reductases / antagonists & inhibitors*
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Tyrosine / chemistry
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Tyrosine / metabolism
Substances
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Enzyme Inhibitors
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Free Radicals
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Iron Chelating Agents
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Peptides, Cyclic
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desferriexochelin 772SM
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exochelins
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Tyrosine
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DNA
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Ribonucleotide Reductases
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Deferoxamine