Title | Synthesis and Biological Evaluation of Fluorescent Bryostatin Analogues. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Cummins TJ, Kedei N, Czikora A, Lewin NE, Kirk S, Petersen ME, McGowan KM, Chen J-Q, Luo X, Johnson RC, Ravichandran S, Blumberg PM, Keck GE |
Journal | Chembiochem |
Volume | 19 |
Issue | 8 |
Pagination | 877-889 |
Date Published | 2018 Apr 16 |
ISSN | 1439-7633 |
Abstract | 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. |
DOI | 10.1002/cbic.201700655 |
Alternate Journal | Chembiochem |
PubMed ID | 29424951 |
Submitted by kej2006 on June 6, 2018 - 4:13pm