Synthesis of EF24−Tripeptide Chloromethyl Ketone: A Novel Curcumin-Related Anticancer Drug Delivery System
| Autor: | Aiming Sun, James P. Snyder, Dennis C. Liotta, Yang J. Lu, Mamoru Shoji |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Curcumin Cell Antineoplastic Agents Apoptosis Factor VIIa Endocytosis Amino Acid Chloromethyl Ketones Thromboplastin Tissue factor Drug Delivery Systems Cell Line Tumor Drug Discovery medicine Humans Cytotoxicity Cell Proliferation Chemistry Cell Cycle medicine.anatomical_structure Biochemistry Cell culture Cancer cell Drug delivery Cancer research Molecular Medicine Drug Screening Assays Antitumor Drug carrier Oxidation-Reduction |
| Zdroj: | Journal of Medicinal Chemistry. 49:3153-3158 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm051141k |
| Popis: | The blood coagulation cascade includes a step in which the soluble protein, factor VIIa (fVIIa), complexes with its transmembrane receptor, tissue factor (TF). The fVIIa/TF protein-protein complex is subsequently drawn into the cell by endocytosis. The observation that TF is aberrantly and abundantly expressed on many cancer cells offers an opportunity to specifically target those cells with an effective anticancer drug. Thus, we propose a new drug delivery system, drug-linker-Phe-Phe-Arg-mk-fVIIa, which can associate with TF on the surface of cancer cells, but release the cytotoxic agent in the cytoplasm. Synthetic procedures have been developed for the preparation of phenylalanine-phenylalanine-arginine chloromethyl ketone, (FFRck) followed by coupling with the cytotoxin EF24 and subsequently fVIIa to give EF-24-FFRmk-fVIIa. When breast cancer cells (MDA-MB-231) and human melanoma cells (RPMI-7951) are treated with the complex, the cells are arrested to a greater extent than EF24 alone by comparison with controls. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|