Dr. Townsend is an expert in the chemical synthesis of biologically important molecules. A major topic of interest is the synthesis of homogeneous human milk oligosaccharides and related constructs to investigate their use as prebiotics in infant formula. He has numerous publications in premier international journals, including Proceedings of the National Academy of Science (USA), Angewandte Chemie International Edition and Journal of the American Chemical Society.
Our research focuses on developing new tools to broaden our fundamental understanding of chemistry while addressing problems significant to human health. To achieve this objective, we divide our efforts between two broadly defined areas, bio- and glycoconjugate assembly and natural product total synthesis. Since our goal is to interface our synthetic efforts with issues of therapeutic application, we value interdisciplinary collaborations with biologists who aid in evaluation of the molecules we prepare. This approach, which is fostered by the Vanderbilt Institute of Chemical Biology, is a critical aspect of our program.
I. Synthesis & Evaluation of Human Milk Oligosaccharide & Related Glycoconjugates
The 3rd largest component of breast milk, human milk oligosaccharides (HMOs) represent a large group of heterogeneous glycans, which can incorporate well above thirty residues per molecule. Because HMOs are largely indigestible, glycans with shorter chains are believed to serve as prebiotics that stimulate the growth of beneficial bacteria in the infant gut. HMOs with longer chains are believed to mimic carbohydrates on the intestinal surface where they serve as decoys for pathogenic bacteria. Due to the sheer volume of structures produced, it is unclear what structures (and in what quantity) are required to obtain the beneficial effects of breast milk.
Since the development of new approaches to assemble glycoconjugates is a major point of interest in our lab, this program will study the glycobiology of human milk by synthesizing homogeneous human milk oligosaccharides (HMOs), and related constructs, to investigate their use as pro- and antibiotics in infant formula. Globally, we view this program as an opportunity to use synthetic organic chemistry to control the composition of the infant gut flora and influence other biological processes.
II. Site-Specific Protein Modifications
The biological roles of proteins are often determined by their co- and post-translational modifications. The resulting constructs play a fundamental role in an array of biological processes varying from mediating protein folding to cell recognition. Because most strategies for chemical protein modification rely on manipulation of nucleophilic amino acid side chains such as lysine or cysteine, our lab seeks to expand the reaction space this process occupies by developing new strategies for site-specific protein modification.
III. Natural Product Total Synthesis
Our total synthesis projects are designed to challenge the state-of-the-art in organic synthesis. We choose target molecules that are structurally unique such as cyclic peptides that incorporate unnatural amino acids and terpenes featuring C- and/or O-glycosylation. Moreover, each target we select has interesting, unstudied biological properties (e.g. anticancer, antibacterial, and immunosuppression). Ultimately, it is our goal to synthesize compounds that can be used as tools to answer greater biological questions or provide a starting point for the development of therapeutics.