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Accelerating the discovery of biologically active small molecules using a high-throughput yeast halo assay.

Authors
  • Nc, Gassner
  • Cm, Tamble
  • Je, Bock
  • N, Cotton
  • Kn, White
  • K, Tenney
  • Rp, St Onge
  • Mj, Proctor
  • G, Giaever
  • C, Nislow
  • Rw, Davis
  • P, Crews
  • Tr, Holman
  • Rs, Lokey
Type
Published Article
Journal
Journal of Natural Products
Publisher
American Chemical Society
Volume
70
Issue
3
Pages
383–390
Source
UCSC Cancer biomedical-ucsc
License
Unknown

Abstract

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 developed a novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The new screen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides a concentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testing materials 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 for bioactivity-guided fractionation, resulting in the identification of crambescidin 800 as a potent antifungal agent.

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