Our lab is interested in developing new bio-orthogonal reactions. These are very special types of reactions that allow imaging of bio-molecules and bio-processes without disturbing the organism under investigation. In general bio-orthogonal reactions have to be inert to a wide range of chemical functionalities present in the cell, such as amines, alcohols, and thiols. They take place in physiological media at neutral pH. All the reagents and the reaction products have to be non-toxic. The reaction has to occur at a reasonable rate at micromolar concentration, which is typical of in vivo imaging. Several reactions have already been developed that satisfy these criteria. One particularly interesting example is an inverse electron demand Diels-Alder reaction between s-tetrazines and trans-cyclooctenes, illustrated below. Royzen lab is interested in developing similar reactions that will allow live cell and animal imaging using fluorescence, MRI, PET, or other non-invasive imaging techniques.
Our lab is also interested in developing molecular probes for live cell imaging of RNA. These probes will allow to answer questions related to RNA biosynthesis, RNA functions on a subcellular level and RNA-protein interactions. For example, one of our collaborators is interested in finding out whether RNA biosynthesis occurs outside of nucleus and mitochondria. Another collaborator wants to visualize viral RNA inside the host cell. The interdisciplinary work on this project involves chemical synthesis of nucleoside analogs, characterization of their photophysical properties, solid phase synthesis of RNA strands containing unnatural nucleosides and live cell imaging. The success of this project will be greatly aided by access to the state-of-the-art analytical instrumentation available at the RNA Institute.
Lastly, our lab is interested in developing small molecule imaging probes for prostate cancer. In 2013, an estimated 238,590 men were diagnosed with prostate cancer in the US and 29,720 succumbed to the disease. Early diagnosis of the disease can substantially improve the survival rates. The design of the imaging probes will be based on known inhibitors of N-acetylated a-linked acidic dipeptidase (NAALADase) a membrane-associated enzyme and a prostate specific membrane antigen (PSMA). Small molecule NAALADase inhibitors described in literature inhibit enzyme activity with IC50s at, or below, 120 nM. Our lab is interesting in chemically modifying these inhibitors to convert them into in vivo imaging probes.