Browsing by Subject "isonitrile-chlorooxime ligation"

Bioorthogonal chemistry and click chemistry have gained tremendous attention during the past few years. They do not refer to a single reaction but to a class of reactions that take inspiration from nature. Click reactions are driven by a strong thermodynamic driving force and therefore they proceed via well-controlled and consistent reaction pathways. Click reactions afford specific products in high yields with negligible by-products. Bioorthogonal chemistry builds on the boundaries set by click chemistry. Bioorthogonal reactions can occur within a living system without interacting or interfering with the natural biological processes therefore both the reactants and the products must be inert and stable under physiological conditions. Bioorthogonal reactions have allowed the real-time study of several biomolecules such as glycans, lipids, nucleic acids, and proteins within living systems without cytotoxicity. In the literature section of the thesis, the most important physical properties of both the isonitrile and chlorooxime are introduced and the most important bioorthogonal reactions for both functionalities are highlighted. The bioorthogonal isonitrile-chlorooxime ligation is discussed in more detail and an example is given of how the ligation can be used to label the cell membrane of living cells with fluorescent moieties. To install a moiety on the cell membrane it must first be modified with small non-natural chemical functionalities also called “chemical reporters.” which can be installed with metabolic oligosaccharide engineering (MOE) using monosaccharide analogues. After installation of the “chemical reporters” onto the cell surface, molecules containing the corresponding bioorthogonal counterpart can be attached to the cell membrane. Lastly, the sulfur(VI) fluoride exchange (SuFEx) click chemistry is discussed. Traditionally, SuFEx click chemistry has been used in organic chemistry to build inorganic connecting bridges between two carbon centres. More recently, SuFEx chemistry has found utility in the radiosynthesis of fluorine-18 containing [18F]sulfonyl fluorides and [18F]fluorosulfates. Fluorine-18 is one of the most commonly used and important positron emitters utilized in radiopharmaceutical chemistry and positron emission tomography (PET). The experimental section of the thesis presents the synthesis routes of the bioorthogonal reaction partners, a peracetylated isonitrilepropanoylmannosamine (Ac4ManNC) and an aryl fluorosulfate chlorooxime. The research hypothesis of the study was that the isonitrile of the Ac4ManNC could be installed onto the cell surface of living Jurkat cells (human T lymphoblast) with MOE. Afterwards, the fluorine-18 labelled aryl [18F]fluorosulfate chlorooxime could have been attached to the cell surface from the isonitrile with the bioorthogonal isonitrile-chlorooxime ligation. This cell surface labelling method could have then been used in the future to research and develop cell therapy treatments by utilizing PET imaging.