Accelerating the Discovery of Biologically Active Small Molecules Using a High-Throughput Yeast Halo Assay

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• 作者：Nadine C. Gassner ; Craig M. Tamble ; Jonathan E. Bock ; Naomi Cotton ; Kimberly N. White ; Karen Tenney ; Robert P. St. Onge ; Michael J. Proctor ; Guri Giaever ; Corey Nislow ; Ronald W. Davis ; Phillip Crews
• 刊名：Journal of Natural Products
• 出版年：2007
• 出版时间：March 2007
• 年：2007
• 卷：70
• 期：3
• 页码：383 - 390
• 全文大小：1018K
• 年卷期：v.70,no.3(March 2007)
• ISSN：1520-6025

文摘

The budding yeast Saccharomyces cerevisiae, a powerful model system for the study of basic eukaryotic cell biology,has been used increasingly as a screening tool for the identification of bioactive small molecules. We have developeda novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The newscreen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides aconcentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testingmaterials including 3104 compounds from the NCI libraries, 167 marine sponge crude extracts, and 149 crude marine-derived fungal extracts. There were 46 active compounds among the NCI set. One very active extract was selected forbioactivity-guided fractionation, resulting in the identification of crambescidin 800 as a potent antifungal agent.