title: Targeting protein-protein interactions and fragment-based drug discovery.
abstract: 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.
authors: Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK.
authors: Eugene
authors: E
authors: Valkov
authors: Tim
authors: T
authors: Sharpe
authors: May
authors: M
authors: Marsh
authors: Sandra
authors: S
authors: Greive
authors: Marko
authors: M
authors: Hyvönen
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D055808:Drug Discovery; D058990:Molecular Targeted Therapy; D011485:Protein Binding / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects*; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries