Coumarin-based fluorescence sensors for detection of neurotransmitters in live cells
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In the central nervous system, neurotransmitters play a critical role in transmitting signals from pre-synaptic vesicles to post-synaptic receptors, enabling proper communication between neurons. For example, glutamate is the most abundant amino acid in the brain and serves as the primary excitatory neurotransmitter. It is fundamental to regulating numerous physiological processes, including memory formation, learning, and synaptic plasticity, such as long-term depression. Dysregulation of glutamate levels has been linked to various neurological disorders, underscoring the need for precise detection and monitoring of this neurotransmitter in biological systems. Fluorescence-based approaches have emerged as powerful non-invasive tools for detecting neurotransmitters due to their high spatial and temporal resolution. These techniques offer significant advantages over traditional methods, such as improved sensitivity, real-time monitoring capabilities, and the ability to study dynamic processes in live cells. Despite these benefits, most existing optical probes for neurotransmitter detection suffer from critical limitations, particularly a lack of selectivity, which hinders their applicability in complex biological environments. In this study, we aim to address these challenges by developing a highly selective fluorescence sensors utilizing a coumarin-3-aldehyde scaffold. The sensing mechanism involves the formation of either iminium ion or/and a boronate ester between the sensor and the target analyte. This design not only enhances binding specificity but also exploits the structural differences between amino acids, enabling accurate detection in complex biological matrices. This innovative approach has the potential to provide valuable insights into neurotransmitter dynamics and pave the way for new diagnostic and therapeutic strategies targeting neurological disorders.
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Ph. D.