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Title: | DESIGN AND SYNTHESIS OF CHEMICAL PROBES FOR IMAGING AND INHIBITOR SCREENING OF TARGETED PROTEINS | Authors: | ZHANG CHONGJING | Keywords: | SNAP, imaging, caspase-1, bromodomains, inhibitor screening, small molecule microarray | Issue Date: | 22-Aug-2013 | Citation: | ZHANG CHONGJING (2013-08-22). DESIGN AND SYNTHESIS OF CHEMICAL PROBES FOR IMAGING AND INHIBITOR SCREENING OF TARGETED PROTEINS. ScholarBank@NUS Repository. | Abstract: | Chemical probes are widely used for live imaging, target identification, inhibitor screenings and so on. This thesis mainly involved three projects. In the first project, a small molecule-assisted protein labeling strategy based on a mutant SNAP-Tag (mSNAP) and its FRET substrate pairs has been developed. Based on this general approach, both one- and two-photon fluorescence microscopic experiments were successfully demonstrated in living cells. However, this approach doesn¿t permit a specific visualization of selected endogenous proteins in living cells. Activity-based probe (ABP) can address this limitation. Thus, in the second project, two different ABPs were designed and synthesized for imaging of Caspase-1 in living systems. Moreover, one ABP probe can greatly improve efficiency and accuracy of the inhibitor screening for Caspase-1. Finally, in the third project, bioorthogonal chemistry between tetrazine and trans-cyclooctene (TCO) was used to generate a small molecule microarray (SMM). Screening this SMM identified potent inhibitors for bromodomains. | URI: | http://scholarbank.nus.edu.sg/handle/10635/49244 |
Appears in Collections: | Ph.D Theses (Open) |
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