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Exploring biology with small organic molecules

Abstract

Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore ‘biological-activity space’. Such strategies involve analysing both protein binding of, and phenotypic responses to, small organic molecules. The mapping of biological-activity space using small molecules is akin to mapping the stars — uncharted territory is explored using a system of coordinates that describes where each new feature lies.

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Figure 1: Comparison of diversity-oriented synthesis (DOS) and focused library synthesis (FLS).
Figure 2: High-throughput-assay formats for detecting small molecule–protein interactions.
Figure 3: Examples of high-throughput phenotypic screens.
Figure 4: Using biological-activity matrices to determine the proteins that regulate phenotypes.

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Acknowledgements

B.R.S. is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.

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Stockwell, B. Exploring biology with small organic molecules. Nature 432, 846–854 (2004). https://doi.org/10.1038/nature03196

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