RESEARCH
Research in the Outlaw Lab integrates synthetic organic chemistry, chemical biology, and biophysics to develop molecular tools and therapeutics that address key challenges in human health. We focus on three core areas: (1) inventing new synthetic methodologies to access underexplored aromatic and heteroaromatic scaffolds with desirable substitution patterns; (2) designing conformationally constrained peptides with enhanced stability, bioavailability, and defined secondary structure to modulate protein-protein interactions; and (3) elucidating and disrupting critical molecular interactions that govern the function of viral proteins. Through these efforts, we aim to expand chemical space, enable precise molecular interrogation of biological systems, and develop next-generation therapeutic strategies.
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 develops new synthetic methodologies to access aromatic and heteroaromatic scaffolds with desirable substitution patterns.
Design of Synthetic Peptides with Enhanced Properties
Peptides possess large surface areas can closely mimic structural features of protein surfaces, making them ideal candidates to modulate protein function and disrupt protein-protein interactions. Despite this potential, the clinical utility of peptides is often limited by poor proteolytic stability, low membrane permeability, and rapid in vivo clearance. The Outlaw Lab develops methods for peptide modification and cyclization to access new classes of conformationally constrained peptides with defined structure and enhanced pharmacokinetic properties to modulate protein-protein interactions.
Elucidation of Critical Molecular Interactions in Viral Proteins
Despite encoding a limited number of proteins, viruses orchestrate complex biochemical processes, including membrane fusion, genome replication and packaging, immune evasion, and viral egress. To accomplish these functions, viruses depend on complex networks of protein-protein interactions (PPIs). Each interaction presents a potential therapeutic target for disrupting the viral life cycle. The Outlaw Lab seeks to elucidate the molecular mechanisms underlying viral protein function and to develop innovative strategies for selectively targeting the PPIs essential for viral infectivity.