We have developed a collection of catalytic methods, broadly defined as the glycosyl cross-coupling, that allows for a stereoretentive (as opposed to stereoinvertive) installation of glycosidic bonds. This departure from established mechanistic paradigms in carbohydrate synthesis opens opportunities for predictable and programmable introduction of glycosides in a broad collection of substrates. Our technology is operational for any saccharide supplied in any anomeric configuration. We have been able to demonstrate the generality of the cross-coupling technology in reactions with free saccharides as well as complex oligosaccharides. We are currently pursuing applications focused on chemical synthesis of bioactive glycoconjugates, bioconjugation, and protein engineering.
Synthesis and Chemical Biology of Thiopeptide Antibiotics
Thiopeptides are post-translationally modified peptides with potent anti-bacterial activities but unrealized clinical potential. We have developed a general approach to access selected members of this family. Our approach capitalizes on cyclodehydration of cysteine residues using a novel molybdenum-based catalyst or cyclic phosphonium anhydrides. With these methods in hand, we were able to complete total syntheses of representative thiopeptide antibiotics and study their biological properties.
In addition to thiopeptides, we actively pursue other targets with validated biological activities. These studies are highly interdisciplinary and involve collaborations with microbiologists, chemical biologists, and medicinal chemists.
Synthetic Protein Assemblies
Synthetic chemistry opens unprecedented opportunities to create and modify complex molecular scaffolds. We design and manufacture protein assemblies that address some of the most challenging problems in gene and drug delivery. Specifically, we prepare macromolecular peptides and protein structures with improved stabilities and low immunogenicity suitable for therapeutic and diagnostic applications. These synthetic proteins are inspired by natural structures but underwent substantial modifications to achieve the desired functions.