The high affinity choline uptake transmembrane protein (CHT) is an important part of the cholinergic transport cycle and yet the structure of this transmembrane protein has still not been determined. The concentration and functionality of choline has been observed to be depleted in neurodegenerative diseases, so obtaining as much data about the cycle is an important part of diagnosis and possible treatment for these diseases, such as Alzheimer's Disease (AD). Previous research has focused on developing extremely sensitive methods of monitoring acetylcholine and choline throughout the uptake process using capillary electrophoresis with electrochemical detection (CEEC). These quantitative methods have provided nonradiochemical strategies for the measurement of choline transport including measurements under conditions of selective cholinergic inhibition.
A cholinomimetic quantum dot (QD) was designed and synthesized to provide qualitative imaging opportunities for monitoring and observing CHT. These QDs were synthesized using a CdSe/ZnSe/ZnS inorganic core in a colloidal organic matrix with trioctylphosphine, trioctylphosphine oxide and hexadecylamine as the coordinating ligands and passivating agents to control growth. The QDs were ~6.2 nm in diameter and exhibited strong and narrow fluorescence intensity and broad UV-absorption properties. The organic ligands were exchanged for water-soluble mercaptosuccinic acid ligands which functionalized the surface with a useful carboxylic acid. An aqueous coupling reaction with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) was utilized to create three distinct functionalized quantum dots; one quantum dot with the –OH moiety on the surface, the second with the quaternary ammonium group on the surface and the third with both functional groups on the surface to work together as a cholinomimetic probe, as the quaternary ammonium and the alcohol groups are the two important groups on choline and the mode of interaction with CHT.
The final cholinomimetic QD was a spherical nanocrystal with a diameter of ~ 6 nm and low polydispersity. The final QDs demonstrated higher fluorescence efficiency than either the –OH QD or the quaternary ammonium QD. The UV spectrum demonstrated retention of the broad absorption properties and dynamic light scattering and TEM confirmed their size and shape.
|Advisor:||Kirchhoff, Jon R.|
|Commitee:||Anderson, Jared, Kirchhoff, Jon, Mason, Mark, Tillekeratne, L. Viranga|
|School:||The University of Toledo|
|School Location:||United States -- Ohio|
|Source:||MAI 56/05M(E), Masters Abstracts International|
|Keywords:||Acetylcholine, Biological imaging, CdSe, Choline, Colloidal synthesis, Quantum dots|
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