The principal focus of our research is to use organic synthesis to study problems of biological and medicinal interest. Several of the templates for our work are found in the vast array of unique substances provided by Nature. Natural products offer the opportunity to advance the art of organic synthesis and enhance our knowledge of chemical reactivity while, at the same time, positioning one to have a significant impact on emerging fields of biology and medicine. We have active and ongoing research efforts in each of the areas described below:
Synthesis, Design, and Study of Peptide Antibiotics that Inhibit Bacterial Cell Wall Biosynthesis
Our work in this area is focused on peptide and depsipeptide antibiotics that interfere with the latter stages of the peptidoglycan biosynthetic pathway. In additional to chemical synthesis, we use computation, solution and solid-state NMR, and biochemical assays in an effort to gain insight into the mode of action utilized by our target compounds. Bacterial resistance is a significant public health problem and our research seeks to identify agents from novel structural classes with unique modes of action.
Peptidoglycan Synthesis and Bacterial Cell Morphology
We have developed, and are continuing to study, fluorescent probes that provide an unprecedented view of the spatiotemporal dynamics of peptidoglycan biosynthesis in real time and in live bacterial cells. These tools have broad utility for the study of peptidoglycan assembly and bacterial cell morphology. We are also actively pursuing the design and preparation of fluorescent probes for specialized optical microscopy applications.
Development of HBV Capsid-binding Probes and Assembly-directed Antivirals
We are actively engaged in the design, synthesis, and evaluation/study of capsid-binding agents that can be modified with fluorescent probes to enable dynamic study of the capsid assembly process in hepatitis B virus (HBV). We are also studying capsid-binding agents that function as antiviral agents. These agents manifest their antiviral activity via capsid defects resulting from acceleration of the capsid-assembly process.