Dec 6, 2012

Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study

ACS Chemical Biology
Lech-Gustav MilroyChristian Ottmann


Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development. As one of the most important "hub" proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention. Here, we summarize recent success stories in small-molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs. The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high-throughput and in silico screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins. Protein-protein interactions (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime. Hence, proteins function not simply as single, isolated entities but display their roles by interacting with other cellular components. These different interaction patterns are presumably as important as the intrinsic biochemical activity status of the protein itself. The biological role of a protein is therefore decisive...Continue Reading

Mentioned in this Paper

Drug Development
Natural Products
Complex (molecular entity)
YWHAQ gene
Plasma Protein Binding Capacity
Staphylococcal Protein A
Therapeutic Agent
Metabolic Inhibition

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