Abstract
Nine azaphilones designated RP-1551-1, -2, -3, -4, -5, -6, -7, -M1, and -M2 were isolated from the culture broth of Penicillium sp. SPC-21609 as inhibitors of PDGF binding to its receptor. RP-1551s inhibit the binding of PDGF AA to the extracellular domain of PDGF alpha-receptor with IC50 values ranging from 0.1 to 2 microM without affecting PDGF BB binding to the extracellular domain of PDGF beta-receptor. PDGF binding was not restored after the PDGF alpha-receptor extracellular domain was washed in an attempt to remove the RP-1551-1 bound to the receptor. This result suggests that RP-1551-1 may irreversibly interact with the PDGF alpha-receptor. Since many azaphilone compounds possess high reactivity with an amino group, RP-1551-1 may prevent PDGF AA binding by reacting with amino groups on the alpha-receptor extracellular domain.
MeSH terms
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Anti-Bacterial Agents / biosynthesis
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / pharmacology*
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Benzopyrans / isolation & purification
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Benzopyrans / pharmacology*
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Culture Media
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Extracellular Space / metabolism
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Fermentation
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Humans
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Penicillium / metabolism*
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Platelet-Derived Growth Factor / metabolism*
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Protein Binding
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Receptor, Platelet-Derived Growth Factor alpha
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor / metabolism*
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Recombinant Proteins / metabolism
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Serum Albumin, Bovine / metabolism
Substances
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Anti-Bacterial Agents
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Benzopyrans
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Culture Media
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Platelet-Derived Growth Factor
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Recombinant Proteins
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Serum Albumin, Bovine
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Receptor, Platelet-Derived Growth Factor alpha
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor