New Fluorophore Scaffolds
Fluorophores are powerful tools for visualizing otherwise invisible structures or processes. Our laboratory is interested in expanding the chemistry of fluorophores to afford new probes and reagents for applications in chemical biology. Towards this goal, we have developed new near-infrared fluorophores that display remarkable brightness and photostability. The installation of novel chemical functionality into these scaffolds allows for the tuning of physical properties, such as cell permeability, as well as the generation of self-reporting small molecule delivery reagents. These scaffolds can be used to develop bioimaging reagents for proteins, small molecules, and post-translational modifications. In addition, these scaffolds are being explored as potential targeted drug delivery reagents.
Protein phosphatases catalyze the removal of phosphate groups from proteins. Importantly, members of this enzyme family are now established as nodes in human disease, making phosphatases attractive targets for the development of diagnostics as well as inhibitors. Our laboratory has described an approach to directly monitor phosphatase activity by employing the phosphorylation-sensitive sulfonamido-oxine (Sox) fluorophore. These Sox-based phosphatase probes can be used to profile perturbations in enzymes derived from cell lysates and tissue homogenates, allowing detailed insight into disease models. In addition, these probes can be used to screen for phosphatase inhibitors.
Protein kinases catalyze the addition of phosphate groups to proteins. This important class of enzymes controls a variety of cellular processes involved in disease development and progression such as inflammation, growth, survival, metabolic, and motility signaling. Through the development and application of new and existing Sox-based probes for protein kinases, our laboratory seeks to profile signaling changes associated with the development and progression of human disease.