Date of Award

1-1-2017

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Chemistry

Content Description

1 online resource (ii, vii, 45 pages) : illustrations (some color)

Dissertation/Thesis Chair

Maksim Royzen

Committee Members

Pan Li, Jan Halamek, Mehmet Yigi

Keywords

Aptamer, Contrast Agent, Smart Contrast Agent, Contrast media (Diagnostic imaging), Dopamine, Biosensors, DNA, Oligonucleotides, Magnetic resonance imaging

Subject Categories

Chemistry

Abstract

A smart contrast agent is a molecule whose relaxivity changes in response to a biological trigger such as a biomolecule, enzymatic activity, or pH. The focus of my graduate project was to develop a DNA aptamer-based smart MRI contrast agent capable of sensing dopamine. Aptamers are single-stranded oligonucleotides that form stable three-dimensional structures efficient in binding with high affinity and specificity for a range of targets. The DNA aptamer has an attached lanthanide-based probe, consisting of a metal ion Gd(III) and a macrocyclic DOTA ligand. The aptamer was assembled using solid phase oligonucleotide synthesis. Nuclear magnetic resonance was used to examine the T1 relaxation times of the DNA aptamer in the present and absence of dopamine. The results showed a decrease of T1 upon incorporation of Gd(III). Addition of dopamine causes an increase in T1 relaxation time, consistent with the hypothesis that the analyte causes conformational changes to the aptamer. The changes in the conformation sterically restrict the coordination sphere around the paramagnetic metal, making it less accessible to water.

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