Isolation and Structure Elucidation of Chlorofusin, a Novel p53-MDM2 Antagonist from a Fusarium sp

Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction of p53 can be caused by increased levels of the protein MDM2, small molecules which antagonize the interaction between these two proteins have potential in cancer therapy. The discovery and structure determination of a...

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Veröffentlicht in:	Journal of the American Chemical Society 2001-01, Vol.123 (4), p.554-560
Hauptverfasser:	Duncan, Sara J, Grüschow, Sabine, Williams, Dudley H, McNicholas, Carole, Purewal, Ravinder, Hajek, Michaela, Gerlitz, Martin, Martin, Steven, Wrigley, Stephen K, Moore, Michael
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - chemistry Antineoplastic Agents - isolation & purification Antineoplastic Agents - pharmacology Drug Interactions Fungal Proteins - chemistry Fungal Proteins - isolation & purification Fungal Proteins - pharmacology Fusarium - chemistry Humans Inhibitory Concentration 50 Molecular Structure Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - metabolism Nuclear Magnetic Resonance, Biomolecular Nuclear Proteins Peptides, Cyclic - chemistry Peptides, Cyclic - isolation & purification Peptides, Cyclic - pharmacology Protein Binding - drug effects Proto-Oncogene Proteins - antagonists & inhibitors Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-mdm2 Tumor Cells, Cultured Tumor Suppressor Protein p53 - metabolism
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Zusammenfassung:	Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction of p53 can be caused by increased levels of the protein MDM2, small molecules which antagonize the interaction between these two proteins have potential in cancer therapy. The discovery and structure determination of a fungal metabolite, chlorofusin, which antagonizes the p53/MDM2 interaction are reported.
ISSN:	0002-7863 1520-5126
DOI:	10.1021/ja002940p