Matching Items (4)

135814-Thumbnail Image.png

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

Description

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

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.

Contributors

Agent

Created

Date Created
  • 2016-05

135407-Thumbnail Image.png

Targeting Tumors: Inclusion of Functional Groups on Ion-Containing Block Copolymers to Combat Cancer

Description

This research attempts to determine the most effective method of synthesizing a peptide such that it can be utilized as a targeting moiety for polymeric micelles. Two melanoma-associated peptides with

This research attempts to determine the most effective method of synthesizing a peptide such that it can be utilized as a targeting moiety for polymeric micelles. Two melanoma-associated peptides with high in vitro and in vivo binding affinity for TNF receptors have been identified and synthesized. Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-ToF) was used to help verify the structure of both peptides, which were purified using Reversed-Phase High Performance Liquid Chromatography (RP-HPLC). The next steps in the research are to attach the peptides to a micelle and determine their impact on micelle stability.

Contributors

Agent

Created

Date Created
  • 2016-05

137623-Thumbnail Image.png

Intelligent Input Parser for Organic Chemistry Reagent Questions

Description

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.

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.

Contributors

Agent

Created

Date Created
  • 2013-05

139859-Thumbnail Image.png

COMBATING CANCER AND ALZHEIMER'S DISEASE: SYNTHESIS OF NOVEL, CHEMOTHERAPEUTIC REXINOIDS

Description

The FDA-approved drug bexarotene has been predominantly utilized for the treatment of cutaneous T-cell lymphoma (CTLC), but has shown promise as an off label treatment for various other cancers as

The FDA-approved drug bexarotene has been predominantly utilized for the treatment of cutaneous T-cell lymphoma (CTLC), but has shown promise as an off label treatment for various other cancers as well as Alzheimer's disease (AD). However, harmful side effects such as hypothyroidism have catalyzed a search for alternative rexinoids which retain similar levels of RXR agonism while reducing the undesirable effects incurred by bexarotene. This honors thesis outlines the steps taken to design and synthesize novel analogues of the selective retinoid-X-receptor (RXR) agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene). Corresponding NMR spectra indicates the successful construction of four novel compounds which are structurally similar to known, biologically-evaluated rexinoids that have induced fewer side effects while stimulating greater levels of RXR selectivity as compared to bexarotene. Future In vitro analyses of these four analogues coupled with the recognized efficacy of their parent compounds demonstrate the chemotherapeutic potential of structurally modified bexarotene analogues

Contributors

Agent

Created

Date Created
  • 2016-05