Drug target discovery and biomarker identification using chemical tools
Chemical probes are key players in searching for a potential druggability of a new molecular target/pathway or process. Particularly, pathfinder molecules in drug discovery projects aid the design and evaluation of biological assay and the identification of useful biomarkers. Here are a few examples of chemical tools that our lab has primarily focused on studying.
1. Activity-based probes to monitor enzyme activity
Activity-based probes (ABPs) react with specific class of enzymes in a manner correlating with enzyme activity, enabling to monitor enzyme function and activity in cells and animals as well as various disease models. In our lab, we aim to develop smart activity-based probes for asparagine endopeptidase (AEP) and high-temperature requirement A (HtRA) serine protease to study the pathogenesis of neurodegenerative diseases.
2. Organelle-targeting peptidomimetics as molecular transporter
Recent advances in gene therapy and antibody drug development have brought renewed attention to molecular transporters as efficient delivery system. In particular, peptoids have unique advantages over other polymeric delivery scaffolds, since they have similar physiological and chemical properties compared to peptides and proteins, while possess superior metabolical and immunological stability. Our goal is to develop novel peptoid scaffolds targeting mitochondria and other cellular organelles for specific delivery of therapeutic agents.
3. Mitochondrial functional modulators for anti-aging therapy
Mitochondria are extraordinary organelles that produce ATP, maintain calcium homeostasis and regulate signal transduction. Mitochondria govern cell growth and proliferation but also mediate cell death. As mitochondria are often called ‘the powerhouses of the cells’, it is not surprising that mitochondrial dysfunction has been linked to a wide variety of disorders, such as cancers, diabetes, and cardiovascular diseases. In our lab, we are interested in developing functional modulators to recover mitochondrial activity in damaged or aging cells, which offer a potential therapeutic option for many age-related diseases.