UC Riverside

Abnormal metabolism is frequently observed in cancer, where the reprogrammed metabolic activities support cancer cells' malignant processes by altering bioenergetics, enhancing biosynthesis, and maintaining redox balance. Understanding the mechanisms of this metabolic reprogramming calls for novel analytical tools for detecting metabolites. This dissertation presents our efforts in developing chemical methods for detecting metabolites. In the first chapter, we present a chemical approach to profile fatty acid uptake in single cells. We demonstrate a surface-based competition assay using azide-modified analogs to probe the fatty acid influx and surface-immobilized dendrimers with dibenzocyclooctyne (DBCO) groups for detection. By integrating this method onto a microfluidics-based multiplex protein analysis platform, we resolved the relationships between fatty acid influx, oncogenic signaling activities, and cell proliferation in single glioblastoma cells. In the second chapter, we present a magnetic particle-based high throughput screening protocol to remove resins with strong non-specific binding from a library. This on-resin preclear method can be used to screen metabolites binders from a peptide library. In the third chapter, we showcase the implementation of the library screening approach for identifying cyclic peptide-based probes for several intracellular metabolites.