Authors

Sining Li

Type

Text

Type

Thesis

Advisor

Parker, Kathlyn | Laughlin, Scott. | Carrico, Isaac.

Date

2017-08-01

Keywords

Chemistry | click chemistry | cyclopropene | dopamine analog | spirocyclopropene

Department

Department of Chemistry.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree

Identifier

http://hdl.handle.net/11401/78345

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Click and bioorthogonal chemistry has been employed in the analysis of many biological systems, but has yet to be extended to the analysis of neural connectivity1. One popular bioorthogonal chemical reporter is the functionalized cyclopropene, which reacts with tetrazines through an inverse electron-demand Diels-Alder reaction2. Here, I describe a strategy for leveraging the cyclopropene-tetrazine ligation for analysis of neural systems and a novel photo-activatable cyclopropene for controlling reactivity in space and time. My first project employs a dopamine analog consisting of a neurotransmitter attached to a cyclopropene tag to study the dopaminergic neural circuit. I designed and synthesized three different cyclopropene-bearing dopamine analogs. These molecules will enable visualization of dopaminergic vesicles and connected neurons, when they are released into the synaptic space. My second project involves developing a new, activatable, bio-orthogonal reagent. I have synthesized a spirocyclopropene that is non-reactive when protected with a light cleavable group, but reactive towards tetrazine reagents one the group is removed by light. Ultimately, this strategy will enable controlled bioorthogonal reactivity that will permit the development of imaging tools for visualizing neural connectivity. | 84 pages

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