Developing high-throughput amenable chemistry for chemical biology applications

Abstract

CATALOMICS is the emerging sub-field of Chemical Biology in which one aims at studying enzymes by employing high-throughput chemistry and technology. The major part of my Ph.D. research concentrates on the development or fine-tuning of high-throughput amenable chemical platform to study enzymes especially Protein Tyrosine Phosphatases (PTPs). We have successfully applied/developed CLICK chemistry, solid-phase amide bond-formation reaction and microwave-assisted synthesis as high-throughput platforms to synthesize libraries of inhibitors targeting various PTPs as well as other vital enzymes. The highlight of all the above described approaches is their simplicity, robustness and the high-quality of the final products. The second part of the thesis demonstrates our successful synthesis and fingerprinting experiments of a novel class of activity-based probes targeting various proteases. The last part of my thesis narrates our successful synthesis of a set of cell permeable small molecule probes for the site-specific labeling of N-terminal cysteine proteins in live cells.