Most biological processes involve permanent and nonpermanent interactions between different proteins. Many protein complexation events play key roles in various human diseases. The thrust of our research focuses on the development of novel, small molecule architectures to reverse a protein's aberrant role, via manipulation of protein complexation events. Numerous protein-protein interfaces contain compact, centralized regions of residues, known as 'hot spots', crucial for interaction. Many proteins function by binding to multiple partners and these proteins tend to use the same hot spots, which can adapt to present the same residues in different structural contexts.
Our research seeks to design and develop scaffolds to artificially suppress or up-regulate specific gene expression profiles via manipulation of protein-protein interactions, thereby inducing therapeutically-beneficial cellular responses in malfunctioning human cells. The proposed research seeks to validate whether protein function can be 'switched' on or off through artificial protein complexation by divalent conjugated small molecule 'hot spot' recognition agents. Molecular modulation of specific protein-protein interactions offers a dynamic approach to artificially regulating aberrant protein activity in human disease. A keen objective of the proposed work is to promote and illuminate the efficacy of developing novel drug-like scaffolds incorporating inorganic, as well as organic, functionality to achieve in vivo manipulation of cellular signaling.