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Design and synthesis of an oligonucleotide-dota conjugate.

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dc.contributor.author Sarsah, Samuel Robert Smith
dc.date.accessioned 2012-04-27T20:42:07Z
dc.date.available 2012-04-27T20:42:07Z
dc.date.created 2005 en_US
dc.date.issued 2012-04-27
dc.identifier.uri http://hdl.handle.net/123456789/967
dc.description ix, 87 leaves en_US
dc.description.abstract Chelates of the macrocycle DOTA and the Gd3 + ion serve as contrast agents for magnetic resonance imaging (MRI). MRI enhancement depends on the concentration of the metal complex agents at the target site. A higher concentration contrast agent gives better enhancement. This can be done by increasing the solubility of agents at the target site, or by increasing the number ofmetal complexes conjugated to a macromolecular agent, or by increasing the cellular uptake of the complex at the target site using molecules that bind to specific cellular receptors. Two Gd3 +-DOTA oligodeoxynucleotide conjugates were synthesized as potential MRI agents. Preparation of the oligodeoxynucleotide decamer was carried out by solid phase synthesis using an ABI 394 DNA Synthesizer. The first oligonucleotide synthesized was destroyed during the purification step. A new DNA decamer oligonucleotide was synthesized and purified. The oligomer was cleaved from the column using ammonia/methylamine 1: 1. Linkers that were conjugated to the oligomer were also synthesized in the lab and characterized with 60MHz NMR. However, the resulting oligomer was also denatured in the lab, so a new oligomer consisting of nine deoxythymidine nucleotides residue was made with the ninth nucleotide derivatized with an amino hexane linker for coupling with DOTA-Nhydroxy-succinamide. This oligomer was purified on poly-pak column. Ultra violet spectroscopy showed a strong absorbance peak at 26Onm. However the Gd-DOTAoligomer conjugate did not have strong absorbance at 260nm. This was attributed to possible interference from Gd-DOTA complex. We intended to couple theIS, 16-0-(isopropylidene)-4, 7,10,13-tetraoxahexadecylamide-folate liker to the Gd-DOTA-oligomer. The purpose is to deliver Gd3 + selectively into tumor cells to enhance tumor imaging and thereby aid in the diagnosis of cancer. However, this was not successful. en_US
dc.language.iso en_US en_US
dc.subject Magnetic resonance imaging. en_US
dc.subject Chelates. en_US
dc.title Design and synthesis of an oligonucleotide-dota conjugate. en_US
dc.type Thesis en_US
dc.college las en_US
dc.department physical sciences en_US

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