WE SEEK TO CREATE MOLECULAR ARCHITECTURES AS TOOLS TO STUDY AND THERAPEUTICS TO TREAT INFECTIOUS DISEASE
Synthetic Methodology to Access New Molecular Scaffolds
Aromatic and heteroaromatic structures are well-represented in bioactive natural products and medicinal chemistry scaffolds. The substitution pattern tolerance and functional group compatibility afforded by traditional synthetic methods, however, limits the chemical space available to researchers exploring these structures. The Outlaw Lab will develop new synthetic methodology to access aromatic and heteroaromatic scaffolds with substitution patterns and functional group tolerance not available with current methods.
Design of Synthetic Peptides with Enhanced Properties
Proteins are made up of polypeptide sequences that adopt three-dimensional structures. Peptides that can mimic specific secondary and tertiary structural elements of proteins have utility as model systems or as inhibitors of protein-protein interactions (PPIs). A major barrier to the development of peptides for therapeutic use has been their poor pharmacokinetic properties (e.g., poor cell permeability, rapid proteolytic degradation). The Outlaw Lab will develop strategies to access peptides with defined three-dimensional architectures and enhanced pharmacokinetic properties.
Disruption of Viral Protein-Protein Interactions
Although the genomes of negative-strand RNA viruses encode only a few proteins, the viruses are able to navigate complex biochemical processes, including fusion with a host cell membrane, replication of the genome, packaging of the genome, evasion of host immune responses, and egress from the host cell. To achieve the necessary functions from such a sparse set of gene products, viruses rely on a complex series of protein-protein interactions (PPIs). Each of these interactions represents a potential therapeutic target for blocking viral infection. The Outlaw Lab will develop strategies to study and, ultimately, disrupt the PPIs required for viral infection.