Protocol for Fragment Hopping

  • Kevin B. Teuscher
  • Haitao JiEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1289)


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.

Key words

Fragment-based drug discovery Fragment hopping Scaffold diversity Isofunctional proteins Protein–protein interactions Inhibitors Selectivity Peptidomimetics 



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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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Chemistry, Center for Cell and Genome ScienceUniversity of UtahSalt Lake CityUSA

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