Manipulations of the Reporter Group for Versatile Applications of Chemical Probes
Date Issued
2015
Date
2015
Author(s)
Tai, Chih-Hsuan
Abstract
The activity-based probes have been widely used in proteomic researches due to its ability to reflect specific enzyme’s activity under certain physiological conditions. We have put a lot of effort into reporter group manipulation for versatile application of chemical probes. We reported three kinds of developments in this dissertation. First, design, synthesis and application of turn-on fluorescent probes for imaging steroid sulfatase activities in cells. Secondly, development and application of fluorous catalysts. Thirdly, development of isotope-coded ABPs for quantitative profiling of serine hydrolase. In the first part, we have designed two turn-on fluorescent probes targeting steroid sulfatase which are designed to generate immobilized fluorescent signal upon hydrolysis. Confocal fluorescence imaging experiments were carried out and compared the results to commercially available imaging reagent. The second part includes development of organo- and organometallic fluorous catalysts. Due to the characters of easy separation, fluorous chemistry is widely utilized in organic synthesis. We have developed new fluorous-taged catalysts and carried catalytic reactions under microwave irradiation. These catalysts did offer better efficiency in purification and matched the statements of green chemistry. The last part is the development of isotope-coded ABPs which applied for quantitative profiling of SHs. We envisioned this design would benefit from MS analysis platform that ensure the in-depth study of complex proteomes.
Subjects
activity-based probes
sulfatase
fluorogenic probes
confocal fluorescence microscopy
fluorous catalyst
microwave reaction
green chemistry
serine hydrolase
ICAT
Type
thesis