Synthetic caged DAG-lactones for photochemically controlled activation of protein kinase C.
Synthetic caged DAG-lactones for photochemically controlled activation of protein kinase C.
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用于光化学控制蛋白激酶的光化学激活的合成笼式dag-lactones。
DOI：
10.1002/cbic.201000670
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发表时间：
2011-03-07
期刊：
影响因子：
--
通讯作者：
Tamamura H
中科院分区：
文献类型：
--
作者：
Nomura W;Narumi T;Ohashi N;Serizawa Y;Lewin NE;Blumberg PM;Furuta T;Tamamura H
与有机小分子相互作用相关的信号转导途径引起了化学生物学领域的极大兴趣。为了详细研究生物活性化合物的作用，有必要消除多种联合作用引起的信号复杂性。“笼状”化合物的开发是解决这一问题的有力工具，当药效团被光激活部分阻断时，这种化合物就不活跃了。通过光照射细胞内的一个有限区域，可以随着时间的推移观察到该位置的配体的特定作用。已经开发了几种“笼化”分子的策略，每种方法都有其自身的优势。蛋白激酶C （PKC）异构体在内源性第二信使1,2 -二酰基甘油（DAG）介导的生长因子和氧化应激的生理反应中起关键作用。这些反应调节了许多细胞过程，包括增殖、[3]分化、[4]迁移、[5]和凋亡促进肿瘤的佛波酯是DAG的有效类似物，为PKC的功能提供了方便的探测。PKC中与C1b结构域结合的配体导致其膜易位。PKC的易位对其功能至关重要，因为PKC的定位决定了它可以进入的底物尽管PKC激活的调控机制复杂，但在同工酶特异性功能的理解上已经取得了相当大的进展PKC同工酶高特异性配体的开发一直是医药领域的一个关键问题。[9a-b]增强
The signal transduction pathways associated with interactions with small organic molecules attract great interest in the field of chemical biology. To study the action of bioactive compounds in detail, it is necessary to eliminate the signaling complexity caused by multiple combined effects. The development of “caged” compounds, which are not active when the pharmacophore is blocked by a photoactivatable moiety, has been a powerful tool with which to approach this problem. Triggered by photoirradiation to a limited area in the cell, the specific effects of the ligand in that location can then be observed over time. Several strategies for “caging” molecules have been developed and each approach has its own advantages.[1]The protein kinase C (PKC) isoforms play pivotal roles in physiological responses to growth factors and oxidative stress mediated through the endogenous second messenger 1, 2-diacylglycerol (DAG). These responses regulate numerous cellular processes,[2] including proliferation,[3] differentiation,[4] migration,[5] and apoptosis.[6] The tumor-promoting phorbol esters, potent analogues of DAG, have provided a convenient probe of PKC function. Ligand binding to the C1b domain in PKC leads to its membrane translocation. The translocation of PKC is of central importance for its function because the localization of PKC determines the substrates to which it has access.[7] Despite the complex regulatory mechanisms of PKC activation, considerable progress in understanding isozyme-specific functions has been made.[8] Development of ligands with high specificities for PKC isozymes has been a critical issue in the medicinal field.[9a–b] Enhancement of the
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影响因子：
5.2
作者：
Furuta, Toshiaki;Watanabe, Takayoshi;Matsuba, Chie
通讯作者：
Matsuba, Chie
影响因子：
3.2
作者：
Geissler, D;Kresse, W;Hagen, V
通讯作者：
Hagen, V
DOI：
10.1073/pnas.96.4.1193
发表时间：
1999-02-16
影响因子：
11.1
作者：
Furuta, T;Wang, SSH;Tsien, RY
通讯作者：
Tsien, RY
DOI：
10.1084/jem.184.6.2399
发表时间：
1996-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ghayur T;Hugunin M;Talanian RV;Ratnofsky S;Quinlan C;Emoto Y;Pandey P;Datta R;Huang Y;Kharbanda S;Allen H;Kamen R;Wong W;Kufe D
通讯作者：
Kufe D
影响因子：
3.5
作者：
Montgomery, HJ;Perdicakis, B;Guillemette, JG
通讯作者：
Guillemette, JG