Synthesis, conformational analysis, and biological evaluation of 1-hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes.
Synthesis, conformational analysis, and biological evaluation of 1-hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes.
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DOI：
10.1021/jm0706719
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发表时间：
2008-01
影响因子：
7.3
通讯作者：
Ryo C. Yanagita;Y. Nakagawa;N. Yamanaka;K. Kashiwagi;N. Saito;K. Irie
中科院分区：
文献类型：
--
作者：
Ryo C. Yanagita;Y. Nakagawa;N. Yamanaka;K. Kashiwagi;N. Saito;K. Irie
传统和新型蛋白激酶C（PKC）同工酶是肿瘤促进剂的主要靶点。我们开发了1-hexylindolactam-V10（5）作为新型PKC同工酶的选择性激活剂，这些同工酶在与肿瘤促进、心脏缺血-再灌注损伤和阿尔茨海默病相关的各种细胞过程中发挥重要作用。该化合物以三种构象异构体的混合物形式存在。5的反式酰胺限制性类似物（14和15）几乎不与PKC同工酶结合，表明5的活性构象可能是顺式酰胺。在HeLa细胞中，化合物5在0.1-1 μ M下相对于常规PKC同工酶选择性地易位新型PKC同工酶。这些结果表明，5可能是有用的新的PKC同工酶的功能分析。
Conventional and novel protein kinase C (PKC) isozymes are the main targets of tumor promoters. We developed 1-hexylindolactam-V10 ( 5) as a selective activator for novel PKC isozymes that play important roles in various cellular processes related to tumor promotion, ischemia--reperfusion injury in the heart, and Alzheimer's disease. The compound existed as a mixture of three conformers. The trans-amide restricted analogues of 5 ( 14 and 15) hardly bound to PKC isozymes, suggesting that the active conformation of 5 could be that with a cis-amide. Compound 5 selectively translocated novel PKC isozymes over conventional PKC isozymes in HeLa cells at 0.1-1 microM. These results suggest that 5 could be useful for the functional analysis of novel PKC isozymes.