Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome
Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome
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DOI：
10.1039/c0mb00326c
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Yoshida, Minoru
中科院分区：
文献类型：
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作者：
Arita, Yuko;Nishimura, Shinichi;Yoshida, Minoru
小分子细胞靶标的鉴定是开发生物工具和药物先导的主要挑战。在这里，我们报告了一种新的基于微阵列的系统，用于识别小分子的靶标或靶标途径，该系统使用一组药物过敏的裂变酵母菌株，这些酵母菌株在开放阅读框组中集体过表达每个基因。这种方法的主要优点是，它提供了全基因组的询问，但需要相对少量的测试化合物。使用该系统，我们鉴定了28个与依托泊苷敏感性相关的基因，其中包括药物靶拓扑异构酶II的基因和其他调节依托泊苷耐受性的似是而非的因素。因此，我们的方法可以加速小分子靶标识别的过程，这有可能揭示具有临床意义的高度保守基因。
Identification of the cellular target of small molecules is a major challenge to developing biological tools and drug leads. Here we report a novel microarray-based system for identification of the target or the target pathway of small molecules using a set of drug-hypersensitive fission yeast strains that collectively overexpress each gene in the open reading frame-ome. The major advantage of this method is that it provides genome-wide interrogation but requires a relatively small amount of the test compound. Using this system, we identified 28 genes linked to etoposide sensitivity, which included genes for the drug target topoisomerase II and other plausible factors that regulate etoposide tolerance. Thus, our approach can accelerate the process of target identification of small molecules, which has the potential to reveal highly conserved genes of clinical relevance.