Development of small molecule fluorescent probes for application in neuroscience
No Thumbnail Available
Authors
Meeting name
Sponsors
Date
Journal Title
Format
Thesis
Subject
Abstract
Herein, we develop a series of selective fluorescent sensors based on coumarin and quinolone core designed to image neurotransmitters catecholamines, glutamate and to distinguish between D-/L-amino acids. Included are the main design strategy, synthesis, spectroscopic data (UV/Vis and fluorescence) and their applications in cells and tissue. NeuroSensor 570 (NS570) was designed and synthesized as a cell impermeable sensor with two binding sites to be able to distinguish between glutamate and GABA. Formation of both an iminium ion and a boronate ester gave high affinity upon binding NS570 to glutamate. Because the sensor is charged, one of the possible applications of the sensor is to be able to study vesicle recycling. While the slower binding kinetics of the sensor with glutamate makes it unsuitable to study fast vesicle recycling, its applicability in labeling hippocampal neurons was reported. A series of pH-dependent sensors was developed to label catecholamines and to report their exocytosis. ES525 was developed using FITC as the base fluorophore. The probe gave good fluorescence enhancement upon pH change from acidic to basic, however it failed to give good labeling of chromaffin cells. ES450, based on a coumarin fluorophore, gave greater fluorescence enhancement and a better binding with catecholamines. The labeling of chromaffin cells by ES450 was inconsistent and could not be used further. Finally, (S)-39 and (R)-39 were developed to distinguish between D-/L-amino acids. Because of only one binding site the probes exhibited only a slight difference in fluorescence between the enantiomers. The development of probe with two binding sites will provide a better fluorescence difference as only one of the enantiomers will be able to bind to the secondary site.
Table of Contents
DOI
PubMed ID
Degree
Ph. D.