Small Molecule Modulators of Protein-Protein Interactions: Selected Case Studies

Some case studies for small molecule modulators of protein-protein interactions (PPI) are reviewed. It has been shown that in general natural products are proven to be highly effective in modulating PPI, and in many cases, this is achieved through the interactions utilizing the allosteric sites. As shown through some specific case studies, the structural information about the PP interface has also been highly useful in designing synthetic compounds. There is a growth in activity in building chemical toolboxes having compounds that are closer to bioactive natural products. This would also challenge the synthetic community to develop new approaches to access a wide variety of natural product-like or natural product inspired scaffolds. One such area that is gaining momentum is to establish methods that allows building the macrocyclic-based chemical toolboxes. Discovery of functional small molecule modulators of PPI demands a close interaction of the synthesis community working closely with other skill sets that are specialized in various aspects of studying these interactions.