Abstract
Five new asterriquinone analogs (2-4, 6, 7), together with previously identified neoasterriquinone (1) and isoasterriquinone (5), were isolated from a fermentation broth of the fungus Aspergillus candidus and purified by HSCCC (high speed counter current chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR and MS/MS techniques. All seven showed inhibitory activity against the binding of a recombinant protein containing the SH2 protein domain of Grb-2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase. Some of these asterriquinones exhibited specific inhibition of Grb-2 binding compared to Grb-7 and PLC-gamma.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Antibiotics, Antineoplastic / isolation & purification
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Antibiotics, Antineoplastic / metabolism
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Antibiotics, Antineoplastic / pharmacology*
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Aspergillus / metabolism*
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Carrier Proteins / antagonists & inhibitors*
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Cell Line
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Chromatography, High Pressure Liquid
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Enzyme-Linked Immunosorbent Assay
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ErbB Receptors / metabolism*
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Fermentation
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Glutathione Transferase / metabolism
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Humans
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Immunoblotting
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Indoles / isolation & purification
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Indoles / metabolism
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Indoles / pharmacology
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Magnetic Resonance Spectroscopy
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Phosphorylation
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Protein Binding
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Spectrometry, Mass, Fast Atom Bombardment
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Spectrophotometry, Ultraviolet
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Antibiotics, Antineoplastic
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Carrier Proteins
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GRAP2 protein, human
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Indoles
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asterriquinone
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Glutathione Transferase
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ErbB Receptors