dc.contributor.advisor | Glass, Timothy | eng |
dc.contributor.author | Zhang, Le | eng |
dc.date.issued | 2019 | eng |
dc.date.submitted | 2019 Summer | eng |
dc.description | Includes vita | eng |
dc.description.abstract | Herein, we develop a series of selective fluorescent sensors based on a quinolone core designed to image neurotransmitters catecholamines, serotonin and glutamate. Included are the main design strategy, synthesis, spectroscopic data (UV/Vis and fluorescence) and their applications in cells and tissue. NeuroSensor 510 (NS510) was designed and synthesized as a selective sensor for imaging norepinephrine. Formation of both an iminium ion and a boronate ester gave high affinity upon binding NS510 to norepinephrine. The sensor was able to label norepinephrine vesicles in chromaffin cells to give punctate staining. Moreover, the sensor was able to monitor norepinephrine exocytosis via correlation of total internal reflective fluorescence (TIRF) microscopy and amperometry. A NIR fluorescent sensor NS659 was developed based on the structure of NS510. Several different synthetic routes were attempted before the sensor was successfully prepared. Upon binding to serotonin, the sensor gave a relatively high affinity but with quenched fluorescence. Initial tests showed that the sensor could be used to label vesicles. Finally, a molecular sensor NS560 was developed to image glutamate. Fluorescence titrations showed that the sensor bound to glutamate to give a very large turn-on response. More importantly, the sensor should be able to differentiate glutamate from GABA due to the difference both in the emission wavelength and the fluorescence response. We tested this sensor in photoreceptor cells and observed that vesicles were labeled by this sensor. Destaining of the vesicles was observed via TIRF microscopy. Also, the sensor can label glutamate in cultured glutamatergic neurons, astrocytes and cortex brain. | eng |
dc.description.bibref | Includes bibliographical references. | eng |
dc.format.extent | 1 online resource (xiv, 165 pages) ; illustrations | eng |
dc.identifier.uri | https://hdl.handle.net/10355/79803 | |
dc.identifier.uri | https://doi.org/10.32469/10355/79803 | eng |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | OpenAccess. | eng |
dc.rights.license | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. Copyright held by author. | |
dc.subject.discipline | Chemistry | eng |
dc.subject.other | Neurotransmitters catecolamines | eng |
dc.subject.other | Serotonin | eng |
dc.subject.other | Glutamate | eng |
dc.subject.other | Fluorescent sensors | eng |
dc.subject.other | Total internal reflective fluorescence | eng |
dc.subject.other | Chemistry | eng |
dc.title | Development of selective high-affinity fluorescent sensors for imaging neurotransmitters and application in cells and tissue | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Chemistry (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph. D. | eng |