Developing Small-molecule Chemical Biology Tools For Studying Cellular Phosphorylation Events In Vivo

Abstract

Amongst all the cellular signaling pathways, protein phosphorylation is one of the more well-studied signaling mechanisms, mediated by a duo of enzymes ¿ kinases which are responsible for phosphorylation that initiates these signals and phosphatases which are responsible for dephosphorylation that terminates these signals. Aberrant regulation of the participants of the phosphoproteome network has been implicated in a number of cancer-related diseases. A major challenge in understanding protein phosphorylation is the sheer complexity of the phosphoproteome network and the fact that precise timing and spatial aspects of protein phosphorylation are crucial to cell functioning. This thesis highlights the advances in the development of small-molecule based chemical biology tools used to study protein phosphorylation. These applications will be demonstrated with novel strategies and designs of protein biosensor for explicit understanding on protein localizations and its functions, in hope to ultimately lead to protein substrate identification which could potentially serves as drug target appraisal.