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Synthesis Of 2seu-Rnas And Rna Squares, Xinghua Chen Dec 2016

Synthesis Of 2seu-Rnas And Rna Squares, Xinghua Chen

Chemistry Theses

In this paper, an improved method [1] for the chemical synthesis of 2SeU-RNA was reported using a streamlined strategy employs 2'-O-Thiomopholine-4-carbothioate protecting group. And single step deprotection of the resulting oligoribonucleotide product using 1,2-diamines/toluene under anhydrous conditions would retain the Selenium atom introduced on the 2-possiton of the modified Uracil. The process is doable with most standard heterobase protection and deprotection, it greatly simplifies the synthesis of 2SeU-RNAs and can be applied to other Selenium modified RNAs synthesis. It makes the synthesis of RNA become as simple and efficient as the chemical synthesis of DNA. Furthermore, the design …


An Investigation Of The Dna Interactions Of Polyamine Anthracene Conjugates Under High Ionic Conditions, Khoa Nguyen Dec 2016

An Investigation Of The Dna Interactions Of Polyamine Anthracene Conjugates Under High Ionic Conditions, Khoa Nguyen

Chemistry Theses

Six polyamine anthracene conjugates (Ants) were studied that take advantage of the polyamine transporter system (PTS) to target specific cancer. The structural features of the Ants involve planar aromatic anthracene that has highly cytotoxicity properties and a polyamine chain similar to natural polyamine, which is taken up by eukaryote cells expressing the PTS actively. Experimental data show that Ants with di-substituted polyamine chains have significantly higher DNA binding affinities than the mono-substituted anthracene conjugates. The high ionic conditions (~150 mM NaCl and 260 mM KCl) in the eukaryote cell nucleus extensively impair the apparent DNA binding of the Ants, but …


Dna Photo-Cleavage And Interactions By Quinoline Cyanine Dyes; Towards Improving Photodynamic Cancer Therapy, Tayebeh Fatemipouya Dec 2016

Dna Photo-Cleavage And Interactions By Quinoline Cyanine Dyes; Towards Improving Photodynamic Cancer Therapy, Tayebeh Fatemipouya

Chemistry Theses

Photodynamic therapy (PDT) is a cancer treatment method in which a photosensitizer, light of a particular wavelength, and also oxygen are used to destroy cancerous cells. Cancer cells absorb the photosensitizing agent which is injected into the body, and it is triggered to cause cell destruction upon absorption of light. This occurs because of the excitation of the photosensitizer produces reactive oxygen species that induce a cascade of cellular and molecular events in the body. Photosensitizing agents that can photo-cleave DNA at long wavelengths are highly demanded in PDT, because the long wavelengths of light can penetrate through tissue deeply …


Exploring Hiv Integrase 3'-Processing Using Designed Dna Substrates And Structural Study Of Hiv Dna Hairpins, Qiushi Li Dec 2016

Exploring Hiv Integrase 3'-Processing Using Designed Dna Substrates And Structural Study Of Hiv Dna Hairpins, Qiushi Li

Chemistry Theses

In the HIV viral integration procedure, 3’-processing of the viral DNA by the integrase enzyme is an essential first step which is followed by the integration of viral DNA into the host genome. In 3’-processing, the integrase cleaves the backbone of the DNA substrate on the 3’ end of a conserved CA dinucleotide motif and inserts a helix between the two DNA strands, forcing them apart (Hare, S., 2012). Our study confirms that the presence of a G-amino group is crucial for 3’-processing. Substituting inosine for G in the CA step removes this amino group and results in loss of …


Optical Property Enhancement And Characterization Of Fluorescent Protein Based Intracellular Calcium Probes, Demesheka Goolsby Aug 2016

Optical Property Enhancement And Characterization Of Fluorescent Protein Based Intracellular Calcium Probes, Demesheka Goolsby

Chemistry Theses

Calcium (Ca2+), a crucial effector for many biological systems, has been associated with diseases such as cardiovascular disease, Alzheimer’s, Parkinson’s, cancer, and osteoporosis. It is important to develop calcium sensors to measure intracellular Ca2+ dynamics at various biological and pathological states. Our lab has engineered such probes by designing a Ca2+ binding site into fluorescent proteins such as Enhanced Green Fluorescent Protein (EGFP) and mCherry. In this thesis, we aim to improve optical properties and metal binding properties of green EGFP-based sensor CatchER and mCherry based red sensors by site-directed mutagenesis and protein engineering, various spectroscopic …


Synthetic Development Of Cyanine Dyes And Investigation Of Their Interaction With Duplex Dna, Cory Holder Aug 2016

Synthetic Development Of Cyanine Dyes And Investigation Of Their Interaction With Duplex Dna, Cory Holder

Chemistry Theses

This thesis outlines two projects that examine interactions between DNA and cyanine dyes: 1) Investigation of monomethine cyanine dye through the synthesis and optical characteristics with a goal to synthetically manipulate these systems to develop a fluorescent biological probe. Several asymmetric and one symmetrical monomethine cyanine dyes were synthetically prepared and their optical properties versus structural changes were explored. Representative dyes were selected for spectroscopically investigating DNA binding to enhance existing probe designs. 2) Early stage development of a non-metalated photosensitizer for photodynamic therapy (PDT) by screening experimentally derived cleavage activities of a number of polymethine cyanine dyes with various …


Synthesis And Determination Of Optical Properties Of Selected Pentamethine Carbocyanine Dyes, Tyler L. Dost Aug 2016

Synthesis And Determination Of Optical Properties Of Selected Pentamethine Carbocyanine Dyes, Tyler L. Dost

Chemistry Theses

This thesis begins with a brief review about the role and importance of the small molecules containing fluorine atoms in medicine and imaging. Then, the first part of the thesis will discuss the synthesis, purification and characterization of pentamethine cyanine dyes. The structure identification of the final dyes is done by using 1H NMR, 13C NMR, 19F NMR, and mass spectrometry. The studies performed after full characterization were the determination of optical and physicochemical properties. After these properties were performed, the fluorophores were evaluated to be good candidates for in vivo testing.


Establishing The Relationship Between Function And Dynamics Within The Gated Mechanism Of D-Arginine Dehydrogenase, Michael Souffrant Aug 2016

Establishing The Relationship Between Function And Dynamics Within The Gated Mechanism Of D-Arginine Dehydrogenase, Michael Souffrant

Chemistry Theses

Enzymes are ubiquitous in biological systems. They catalyze chemical reactions and are involved in many biochemical processes. The enzyme of interest is Pseudomonas aeruginosa D-arginine dehydrogenase (PaDADH). This flavin-dependent enzyme is composed of approximately 375 amino acid residues and has a broad substrate specificity with D-amino acids. A water recognition motif, observed in roughly 1200 non-redundant protein data bank (PDB) structures, was revealed to be embedded near the active site of PaDADH. This motif coincides with the conformational changes of the enzyme’s gated mechanism. Molecular dynamics simulations were carried out to study the gated properties and structural characteristics of PaDADH …


Spectroscopic And Thermodynamic Characterization Of Human 3-Hydroxyanthranilate-3,4-Dioxygenase, Calmour Henry May 2016

Spectroscopic And Thermodynamic Characterization Of Human 3-Hydroxyanthranilate-3,4-Dioxygenase, Calmour Henry

Chemistry Theses

3-Hydroxyanthranilate-3,4-dioxygenase (HAO) is a non-heme iron dependent enzyme that catalyzes the oxidative ring opening of 3-hydroxyanthranilate (HAA) which is an intermediate in the kynurenine pathway and its ring opening is the final enzymatic step from tryptophan to quinolinic acid (QUIN). QUIN functions as an N-methyl-D-aspartate (NMDA) receptor agonist and elevated brain levels of QUIN have been observed in neurodegenerative diseases. Reducing QUIN levels is of pharmacological importance. Kinetic and calorimetric studies were performed on human HAO using UV/Vis spectroscopy and isothermal titration calorimetry to understand its stability and behavior using its natural substrate (3-HAA) and neurological inhibitors such as …


Investigation Of A Novel Mammalian Thiol Dioxygenase Structure: Human Cysteamine Dioxygenase, Tseng Xiong, Tseng Xiong May 2016

Investigation Of A Novel Mammalian Thiol Dioxygenase Structure: Human Cysteamine Dioxygenase, Tseng Xiong, Tseng Xiong

Chemistry Theses

In 2007, a gene homolog of CDO encoded by the gene Gm237 in the DUF164 family was identified as cysteamine dioxygenase (ADO). ADO is one of the only known thiol dioxygenases found in mammals. Both ADO and its partner cysteine dioxygenase (CDO) are non-heme iron dependent enzymes that play a crucial role in the biosynthesis of taruine/hypotaurine by insertion of a dioxygen molecule. However, ADO has been overshadowed by CDO as heavy research focus on CDO over the past decade has led to the elucidation of its structure and possible mechanistic properties. In an effort to further understand ADO’s mechanism …


Modifications To The Benzophenoxazine Architecture: Synthesis And Characterization, Vincent Martinez May 2016

Modifications To The Benzophenoxazine Architecture: Synthesis And Characterization, Vincent Martinez

Chemistry Theses

Nile red and Nile blue are intensely colored fluorescent dyes from the benzophenoxazine family. Modification of the donor amine with varying alkyl substituents was achieved with the principle aim being to investigate differences, both optical and physical, between dye scaffolds outfitted with secondary amines versus tertiary amines. These changes to the dyes’ architectural framework gave holistic effects to the bulk molecule by modulating hydrophobicity, optical properties, and protein binding constants to human serum albumin.


Study Of The Dna Packaging Protein From A Phage That Replicates Under Extreme Conditions, Philip Lessans May 2016

Study Of The Dna Packaging Protein From A Phage That Replicates Under Extreme Conditions, Philip Lessans

Chemistry Theses

Bacteriophages are viruses that infect bacteria. Phage DNA packaging is one process in the assembly of mature phages that is not well characterized. Elucidating the mechanism of this process would enhance our understanding of the biological significance of the machinery. A previous study suggested that the protein gp74 from bacteriophage HK97 functions as an HNH endonuclease and is required for phage DNA packaging. In this thesis the functionality was assessed for a protein from a phage that replicates under extreme conditions. Our data suggest that the endonuclease activity may not be essential for the role of gp74 in phage DNA …