Conformationally constrained analogues of diacylglycerol. 29. Cells sort diacylglycerol-lactone chemical zip codes to produce diverse and selective biological activities
Conformationally constrained analogues of diacylglycerol. 29. Cells sort diacylglycerol-lactone chemical zip codes to produce diverse and selective biological activities
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DOI：
10.1021/jm8001907
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发表时间：
2008-09-11
影响因子：
7.3
通讯作者：
Marquez, Victor E.
中科院分区：
文献类型：
--
作者：
Duan, Dehui;Sigano, Dina M.;Marquez, Victor E.
二酰基甘油-内酯（DAG-内酯）库产生的固相方法使用IRORI技术产生了各种独特的生物活性。在分子的两个区域中化学多样性的微妙差异，其组合产生了我们所称的“化学邮政编码”，能够将相对较小的化学空间转化为更大的生物活动领域，因为细胞内含有膜的细胞器似乎能够解码这些“化学邮政编码”。据推测，结合蛋白激酶C（PKC）同工酶或其他非激酶靶蛋白，含有二酰基甘油响应，膜相互作用域（C1域）后，得到的复合物被定向到不同的细胞内位点，其中不同的底物集访问。多个细胞生物测定表明，DAG-内酯，在体外结合到PKC α不同程度，扩大其生物库到一个更大的域，引发不同的细胞反应。
Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity in two areas of the molecule, the combination of which generates what we have termed "chemical zip codes", are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these "chemical zip codes". It is postulated that after binding to protein kinase C (PKC) isozymes or other nonkinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKC alpha to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses.