Targeting Protein–Protein Interactions and Fragment-Based Drug Discovery

  • Eugene Valkov
  • Tim Sharpe
  • May Marsh
  • Sandra Greive
  • Marko HyvönenEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 317)


Protein–protein interactions (PPI) are integral to the majority of biological functions. Targeting these interactions with small molecule inhibitors is of increased interest both in academia as well as in the pharmaceutical industry, both for therapeutic purposes and in the search for chemical tools for basic science. Although the number of well-characterised examples is still relatively modest, it is becoming apparent that many different kinds of interactions can be inhibited using drug-like small molecules. Compared to active site targeting, PPI inhibition suffers from the particular problem of more exposed and less defined binding sites, and this imposes significant experimental challenges to the development of PPI inhibitors. PPI interfaces are large, up to thousands of square angstroms, and there is still debate as to what part of the interface one should target. We will review recent developments in the field of PPI inhibition, with emphasis on fragment-based methods, and discuss various factors one should take into account when developing small molecule inhibitors targeted at PPI interfaces.


Biophysical screening Fragment-based drug discovery Inhibitor Protein–protein interactions Structural biology 



This work was funded by The Wellcome Trust under Seeding Drug Discovery Initiative and the Strategic Award scheme.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Eugene Valkov
    • 1
  • Tim Sharpe
    • 1
  • May Marsh
    • 1
  • Sandra Greive
    • 1
  • Marko Hyvönen
    • 1
    Email author
  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK

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