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Exploration of Enzymatic Efficiency in Double-Stranded DNA by Uracil-DNA Glycosylase and Optimization of Glycosylation Reaction of DNA Precursor

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The two chapters of this thesis focus on different aspects of DNA and the properties of nucleic acids as the whole. Chapter 1 focuses on the structure of DNA and its relationship to enzymatic efficiency. Chapter 2 centers itself on

The two chapters of this thesis focus on different aspects of DNA and the properties of nucleic acids as the whole. Chapter 1 focuses on the structure of DNA and its relationship to enzymatic efficiency. Chapter 2 centers itself on threose nucleic acid and optimization of a step in the path to its synthesis. While Chapter 1 discusses DNA and Uracil-DNA Glycosylase with regards to the base excision repair pathway, Chapter 2 focuses on chemical synthesis of an intermediate in the pathway to the synthesis of TNA, an analogous structure with a different saccharide in the sugar-phosphate backbone.
Chapter 1 covers the research under Dr. Levitus. Four oligonucleotides were reacted for zero, five, and thirty minutes with uracil-DNA glycosylase and subsequent addition of piperidine. These oligonucleotides were chosen based on their torsional rigidities as predicted by past research and predictions. The objective was to better understand the relationship between the sequence of DNA surrounding the incorrect base and the enzyme’s ability to remove said base in order to prepare the DNA for the next step of the base excision repair pathway. The first pair of oligonucleotides showed no statistically significant difference in enzymatic efficiency with p values of 0.24 and 0.42, while the second pair had a p value of 0.01 at the five-minute reaction. The second pair is currently being researched at different reaction times to determine at what point the enzyme seems to equilibrate and react semi-equally with all sequences of DNA.
Chapter 2 covers the research conducted under Dr. Chaput. Along the TNA synthesis pathway, the nitrogenous base must be added to the threofuranose sugar. The objective was to optimize the original protocol of Vorbrüggen glycosylation and determine if there were better conditions for the synthesis of the preferred regioisomer. This research showed that toluene and ortho-xylene were more preferable as solvents than the original anhydrous acetonitrile, as the amount of preferred isomer product far outweighed the amount of side product formed, as well as improving total yield overall. The anhydrous acetonitrile reaction had a final yield of 60.61% while the ortho-xylene system had a final yield of 94.66%, an increase of approximately 32%. The crude ratio of preferred isomer to side product was also improved, as it went from 18% undesired in anhydrous acetonitrile to 4% undesired in ortho-xylene, both values normalized to the preferred regioisomer.

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2016-05

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Intelligent Input Parser for Organic Chemistry Reagent Questions

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Due to its difficult nature, organic chemistry is receiving much research attention across the nation to develop more efficient and effective means to teach it. As part of that, Dr. Ian Gould at ASU is developing an online organic chemistry

Due to its difficult nature, organic chemistry is receiving much research attention across the nation to develop more efficient and effective means to teach it. As part of that, Dr. Ian Gould at ASU is developing an online organic chemistry educational website that provides help to students, adapts to their responses, and collects data about their performance. This thesis creative project addresses the design and implementation of an input parser for organic chemistry reagent questions, to appear on his website. After students used the form to submit questions throughout the Spring 2013 semester in Dr. Gould's organic chemistry class, the data gathered from their usage was analyzed, and feedback was collected. The feedback obtained from students was positive, and suggested that the input parser accomplished the educational goals that it sought to meet.

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2013-05

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Design and Isolation of a Novel Phosphine Functionalized Carbodiimide as a Versatile Precursor to Accessing Hemilabile Amidinate and Guanidinate Ligands

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Amidinates and guanidinates are promising supporting ligands in organometallic and coordination chemistry, highly valued for their accessibility, tunability, and comparability with other popular anionic N-chelating hard donor ligands like β-diketiminates. By far the most powerful way to access these ligands

Amidinates and guanidinates are promising supporting ligands in organometallic and coordination chemistry, highly valued for their accessibility, tunability, and comparability with other popular anionic N-chelating hard donor ligands like β-diketiminates. By far the most powerful way to access these ligands involves direct metal-nucleophile insertion into N,N’- substituted carbodiimides. However, the majority of reported examples require the use of commercially accessible carbodiimide peptide coupling reagents with simple alkyl substituents leading to low variation in potential substituents. Presented here is the design, synthesis, and isolation of a novel N,N’-bis[3-(diphenylphosphino)propyl]carbodiimide via an Aza-Wittig reaction between two previously described air stable substrates. At room temperature, 3-(diphenylphosphanyl-borane)-propylisocyanate was added to N-(3-(diphenylphospino)propyl)-triphenylphosphinimine, leading to product formation in minutes. One-pot phosphine-borane deprotection, followed by simple filtration of the crude mixture through a small, basic silica plug using pentane and diethyl ether granted the corresponding carbodiimide in high purity and yield (over 70%), confirmed by 1H, 13C, and 31P NMR spectroscopy. In addition to accessing different central carbon substituents, modification of phosphine substituents should be easily accessible through minor variations in the synthesis. With these precursors, anionic amidinates and guanidinates capable of κ4 -N,N,P,P-coordination may be accessed. The ability of the labile phosphine arms to associate and dissociate may facilitate catalysis. Thus, this carbodiimide provides a tunable, reliable one step precursor to novel substituted amidinates and guanidinates for homogeneous transition metal catalysis.

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2022-05

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Syntheses of Non-Canonical Amino Acids Containing Stilbene

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Non-canonical amino acids (NCAAs) can be used in protein chemistry to determine their structures. A common method for imaging proteins is cryo-electron microscopy (cryo-EM) which is ideal for imaging proteins that cannot be obtained in large quantities. Proteins with indistinguishable

Non-canonical amino acids (NCAAs) can be used in protein chemistry to determine their structures. A common method for imaging proteins is cryo-electron microscopy (cryo-EM) which is ideal for imaging proteins that cannot be obtained in large quantities. Proteins with indistinguishable features are difficult to image using this method due to the large size requirements, therefore antibodies designed specifically for binding these proteins have been utilized to better identify the proteins. By using an existing antibody that binds to stilbene, NCAAs containing this molecule can be used as a linker between proteins and an antibody. Stilbene containing amino acids can be integrated into proteins to make this process more access able. In this paper, synthesis methods for various NCAAs containing stilbene were proposed. The resulting successfully synthesized NCAAs were E)-N6-(5-oxo-5-((4-styrylphenyl) amino) pentanoyl) lysine, (R,E)-2-amino-3-(5-oxo-5-((4-styrylphenyl)amino)pentanamido)propanoic acid, (E)-2-amino-5-(5-oxo-5-((4-styrylphenyl) amino) pentanamido) pentanoic acid. A synthesis for three more shorter amino acids, (R,E)-2-amino-3-(3-oxo-3-((4-styrylphenyl) amino) propanamido) propanoic acid, (E)-2-amino-5-(3-oxo-3-((4-styrylphenyl) amino) propanamido) pentanoic acid, and (E)-N6-(3-oxo-3-((4-styrylphenyl) amino) propanoyl) lysine, is also proposed.

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2022-05