Fluorescent Probes of the Apoptolidins and their Utility in Cellular Localization Studies
| Autor: | Brian O. Bachmann, David W. Piston, Alessandro Ustione, David C. Earl, Aaron T. Jacobs, Sean M. DeGuire, Brenda A. Crews, Lawrence J. Marnett, Katherine M. Chong, Gary A. Sulikowski, Yu Du, Cristina Daniel |
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| Rok vydání: | 2014 |
| Předmět: |
Microscopy
Confocal Disaccharide Antineoplastic Agents Apoptosis General Medicine General Chemistry Mitochondrion Fluorescence Article Catalysis chemistry.chemical_compound Aglycone chemistry Biochemistry Pyrones Cell culture Cell Line Tumor Humans Lipid Peroxidation Macrolides Cytotoxicity Cellular localization Fluorescent Dyes |
| Zdroj: | Angewandte Chemie International Edition. 54:961-964 |
| ISSN: | 1433-7851 |
| DOI: | 10.1002/anie.201408906 |
| Popis: | Apoptolidin A has been described as among the top 0.1% most cell selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties located at C9 and C27, respectively. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analog of apoptolidin A, was produced by targeted glycosyl transferase gene deletion and displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of the C2′ hydroxyl group of apoptolidins A and H with 5-azidopentanoic acid afforded azido functionalized derivatives of potency equal to their parent macrolide. Azido apoptolidins readily underwent strain-promoted alkyne azido cycloaddition (SPAAC) reactions to provide access to fluorescent and biotin functionalized probes. Microscopy studies demonstrate apoptolidins A and H localize in the mitochondria of H292 human lung carcinoma cells. |
| Databáze: | OpenAIRE |
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