Expanding the functional group compatibility of small-molecule microarrays: Discovery of novel calmodulin ligands
Expanding the functional group compatibility of small-molecule microarrays: Discovery of novel calmodulin ligands
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DOI：
10.1002/anie.200351043
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Barnes-Seeman, D;Park, SB;Schreiber, SL
来自以多样性为导向的合成(DOS)的小分子扰乱了蛋白质的功能，促进了生物学的探索。小分子微阵列[1a，b，2]已被证明在发现小分子-蛋白质相互作用导致小分子蛋白质功能调节剂方面[3]是可靠和可扩展的[3]。[1，4]氯化载玻片已被用来打印含有伯醇的DOS衍生化合物。[2B]然而，对文献的检查表明，合成路线产生的羧酸库或酚比产生伯醇的合成路线多。[5]在我们自己的实验室中，已经开发出以酚苯甲醛为第一组多样性元素的骨架多样化产品的DOS途径，[6]并且酚类产品不附着在氯化载玻片上。我们现在报告了一种新的方法，用于在玻璃片上捕获酚类化合物以及含有至少具有类似酸性的官能团的化合物。
Small molecules derived from diversity-oriented synthesis (DOS) that perturb the functions of proteins are facilitating explorations in biology. Small-molecule microarrays [1a, b, 2] have proven robust and scalable [3] for the discovery of small-molecule–protein interactions that lead to small-molecule modulators of protein function.[1, 4] Chlorinated slides have been used to print primary-alcohol-containing DOS-derived compounds.[2b] However, inspection of the literature suggests that synthetic routes yielding libraries of carboxylic acids or phenols outnumber those yielding primary alcohols.[5] In our own laboratory, DOS pathways leading to skeletally diverse products that use phenolic benzaldehydes as the first set of diversity elements have been developed,[6] and the phenolic products do not attach to chlorinated slides. We now report a new method for the covalent capture on a glass slide of phenols as well as compounds containing functional groups of at least comparable acidity.