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Synthesis and Biological Evaluation of Fluorescent Bryostatin Analogues
Author(s) -
Cummins Thomas J.,
Kedei Noemi,
Czikora Agnes,
Lewin Nancy E.,
Kirk Sharon,
Petersen Mark E.,
McGowan Kevin M.,
Chen JinQiu,
Luo Xiaoling,
Johnson Randall C.,
Ravichandran Sarangan,
Blumberg Peter M.,
Keck Gary E.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700655
Subject(s) - bryostatin 1 , protein kinase c , u937 cell , biological activity , intracellular , fluorescence , biochemistry , phorbol ester , chemistry , microbiology and biotechnology , biology , kinase , in vitro , physics , quantum mechanics
To investigate the cellular distribution of tumor‐promoting vs. non‐tumor‐promoting bryostatin analogues, we synthesized fluorescently labeled variants of two bryostatin derivatives that have previously shown either phorbol ester‐like or bryostatin‐like biological activity in U937 leukemia cells. These new fluorescent analogues both displayed high affinity for protein kinase C (PKC) binding and retained the basic properties of the parent unlabeled compounds in U937 assays. The fluorescent compounds showed similar patterns of intracellular distribution in cells, however; this argues against an existing hypothesis that various patterns of intracellular distribution are responsible for differences in biological activity. Upon further characterization, the fluorescent compounds revealed a slow rate of cellular uptake; correspondingly, they showed reduced activity for cellular responses that were only transient upon treatment with phorbol ester or bryostatin 1.