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Diversity-oriented synthesis: exploring the intersections between chemistry and biology

Nature Chemical Biology volume 1, pages 74–84 (2005)Cite this article

Abstract

Diversity-oriented synthesis (DOS) is an emerging field involving the synthesis of combinatorial libraries of diverse small molecules for biological screening. Rather than being directed toward a single biological target, DOS libraries can be used to identify new ligands for a variety of targets. Several different strategies for library design have been developed to target the biologically relevant regions of chemical structure space. DOS has provided powerful probes to investigate biological mechanisms and also served as a new driving force for advancing synthetic organic chemistry.

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Figure 7: Separation platforms and library synthesis techniques in diversity-oriented synthesis.
Figure 1: Example of principal component analysis comparison of synthetic drugs and natural products.
Figure 2: Uretupamines, function-selective suppressors of the yeast signaling protein Ure2p.
Figure 3: Tubacin and histacin, paralog-selective histone deacetylase family inhibitors.
Figure 4: Small-molecule modulation of stem cell differentiation.
Figure 5: Fexaramine, a potent non-steroidal agonist of the farnesoid X receptor.
Figure 6: IIA6B17, a small-molecule inhibitor of the Myc-Max protein-protein interaction.

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Acknowledgements

Generous financial support for my laboratory has been provided by the US National Institutes of Health (CA104685), Department of Defense (CM030085), William Randolph Hearst Fund in Experimental Therapeutics, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center.

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    Derek S Tan

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Tan, D. Diversity-oriented synthesis: exploring the intersections between chemistry and biology. Nat Chem Biol 1, 74–84 (2005). https://doi.org/10.1038/nchembio0705-74

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