Almost all projects in the lab are based on the synthesis of organic molecules with new architecture and/or new biological function.
We use synthetic molecules to manipulate DNA, RNA, and proteins for optochemical control of function.
Structure and Activity Relationships - To understand the molecular requirements of the small molecules we identify from high-throughput screens of compound libraries, we conduct extensive structure activity relationship studies in order to improve the activity of our discovered molecules. In addition, we are using the obtained information to construct small molecule probes that we apply to the investigation of microRNA regulation and biogenesis.
Nucleotides - We have assembled a broad range of photocaged nucleotides through multi-step synthetic routes. The caged phosphoramidites are incorporated into DNA and RNA through automated oligonucleotide polymerization chemistry on solid-support. We have demonstrated that we can target all four different bases and that we can apply this approach to the optochemical regulation of antisense agents, DNA decoys, DNA logic gates, and triplex-forming oligonucleotides in mammalian cells and aquatic embryos.
Unnatural Amino Acids - We have developed synthetic routes to a wide range of unnatural amino acids with new functions that are not found in nature. Examples include photocaged amino acids, photocrosslinkers, fluorinated amino acids, and amino acids modified with biophysical probes. We are synthesizing these compounds in order to engineer the function of proteins through site-specific incorporation of unnatural amino acids into the polypeptide chain. The synthetic routes to these amino acids need to be scalable to multi-gram quantities.
Photocontrolled Natural Products - Natural products have evolved over thousands of years to perform very specific biological functions. For example, they can induce gene expression, inhibit ribozyme function, and control protein dimerization. In order to allow for optochemical control over these biological processes, we have developed synthetic routes to several natural products that are site-specifically modified with caging groups. Examples include caged toyocamycin, caged erythromycin, and caged rapamycin.