荧光苔藓抑素类似物的合成与生物评价。
Synthesis and Biological Evaluation of Fluorescent Bryostatin Analogues.
机构信息
University of Utah, Department of Chemistry, 315 South 1400 East, Room 2020, Salt Lake City, UT, 84112, USA.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 4048, Bethesda, MD, 20892, USA.
出版信息
Chembiochem. 2018 Apr 16;19(8):877-889. doi: 10.1002/cbic.201700655. Epub 2018 Mar 25.
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.
为了研究促肿瘤与非促肿瘤的海鞘素类似物的细胞分布，我们合成了两种海鞘素衍生物的荧光标记变体，这两种衍生物在 U937 白血病细胞中以前表现出类佛波醇酯或海鞘素样的生物学活性。这两种新的荧光类似物都显示出与蛋白激酶 C（PKC）结合的高亲和力，并在 U937 测定中保留了未标记母体化合物的基本性质。荧光化合物在细胞内的分布模式相似；然而，这与一种现有的假说相矛盾，即不同的细胞内分布模式是导致生物学活性差异的原因。进一步的特征分析表明，荧光化合物的细胞摄取率较慢；相应地，它们对细胞反应的活性降低，而这些反应在佛波醇酯或海鞘素 1 处理时仅短暂发生。
Zotero 插件