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- Title
Fluorescent Probes of the Apoptolidins and their Utility in Cellular Localization Studies.
- Authors
DeGuire, Sean M.; Earl, David C.; Du, Yu; Crews, Brenda A.; Jacobs, Aaron T.; Ustione, Alessandro; Daniel, Cristina; Chong, Katherine M.; Marnett, Lawrence J.; Piston, David W.; Bachmann, Brian O.; Sulikowski, Gary A.
- Abstract
Apoptolidin A has been described 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. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μ M) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analogue of apoptolidin A, displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of apoptolidins A and H with 5-azidopentanoic acid afforded azido-functionalized derivatives of potency equal to that of the parent macrolide. They also underwent strain-promoted alkyne-azido cycloaddition 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.
- Subjects
MOLECULAR probes; FLUOROPHORES; FLUORESCENCE spectroscopy; DEGLYCOSYLATION; AGLYCONES
- Publication
Angewandte Chemie International Edition, 2015, Vol 54, Issue 3, p961
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201408906