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Protocol for Fragment Hopping

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Book cover Fragment-Based Methods in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1289))

Abstract

Fragment hopping is a fragment-based approach to designing biologically active small molecules. The key of this approach is the determination of the minimal pharmacophoric elements in the three-dimensional space. Based on the derived minimal pharmacophoric elements, new fragments with different chemotypes can be generated and positioned to the active site of the target protein. Herein, we detail a protocol for performing fragment hopping. This approach can not only explore a wide chemical space to produce new ligands with novel scaffolds but also characterize and utilize the delicate differences in the active sites between isofunctional proteins to produce new ligands with high target selectivity/specificity.

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Acknowledgement

This work was supported by the Pulmonary Fibrosis Foundation I.M. Rosenzweig Young Investigator Award (Award number: 235170) and the Department of Defense CDMRP BCRP breakthrough award (W81XWH-13-BCRP-BREAKTHROUGH).

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Correspondence to Haitao Ji .

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Teuscher, K.B., Ji, H. (2015). Protocol for Fragment Hopping. In: Klon, A. (eds) Fragment-Based Methods in Drug Discovery. Methods in Molecular Biology, vol 1289. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2486-8_6

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  • DOI: https://doi.org/10.1007/978-1-4939-2486-8_6

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