Small-molecule inhibitors of protein-protein interactions: how to mimic a protein partner
1Discovery Technologies, Roche Research Center, Nutley, NJ 07110, USA. david.fry@roche.com
Abstract:
This systematic review describes successful examples of small-molecule inhibitors of protein-protein interactions, and compares their binding strategies to those employed by the natural protein partners. It extends and updates an earlier survey of this type (Fry DC, Curr Prot Pep Sci 2008; 9: 240-7). From analysis of these systems, common themes and lessons are presented that may assist future drug discovery efforts involving targets in this class. One encouraging finding is that a wide scope appears to be allowed at these sites in terms of binding strategies and chemotypes, which suggests that the outlook for finding small-molecule protein-protein inhibitors is favorable.
Related Concept Videos
Protein-protein Interfaces
Protein-Protein Interfaces
Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-Drug Binding: Mechanism and Kinetics
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...


