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Medicinal-Pharmaceutical Chemistry Commons

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2016

Theses/Dissertations

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Articles 1 - 16 of 16

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

The Synthesis Of Chemosensors For Toxic Analytes, Johnathan Hugh Broome Aug 2016

The Synthesis Of Chemosensors For Toxic Analytes, Johnathan Hugh Broome

Dissertations

A number of chemosensors have been designed and synthesized to target cations (Zn2+ions), neutral molecules (cathinones), charged molecules (aminoindanes), and anions. The Zn2+ ion sensor featured bistriazole designed binding unit and ferrocene signaling units. Characterization of Zn2+ ion binding was carried out with electrochemical techniques (CV and DPV), 1H-NMR, mass spectrometry, and molecular modelling. It exhibited a 1:1 binding stoichiometry with Zn2+ and had an affinity for ZnCl2 (Log K1:1 = 4.1 ± 0.02) over other Zn2+ salts.

The cathinone probe was designed to selectively bind mephedrone over common ...


Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii Aug 2016

Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii

Dissertations

The studies presented in section 1 (Chapters I-IV) focus on the design and development of nucleic acid four-way junctions (4WJs) to target a member of the high mobility group (HMG) proteins, the proinflammatory cytokine high mobility group box 1 protein (HMGB1). In the present study, hybrid PNA-DNA 4WJs based on a model DNA 4WJ were constructed to improve the thermal stability of 4WJs while maintaining strong binding affinity toward HMGB1. An electrophoretic mobility shift assay (EMSA) was used to examine the binding affinity of an isolated DNA binding domain of HMGB1, the HMGB1 b-box (HMGB1b), toward a set of PNA-DNA ...


Enzyme-Mediated And Mechanistic Investigations Of Tetrahydroisoquinoline Synthesis Through The Pictet-Spengler Reaction, Jordan Elise Fauser Jun 2016

Enzyme-Mediated And Mechanistic Investigations Of Tetrahydroisoquinoline Synthesis Through The Pictet-Spengler Reaction, Jordan Elise Fauser

College of Science and Health Theses and Dissertations

Tetrahydroisoquinolines (THI) are biologically active natural products with applications to a variety of diseases. These compounds also act as precursors for other pharmacologically active natural products. In this investigation, a new synthetic approach for generation of halogenated THIs was proposed. Using cross-linked tyrosinase aggregate, halogenated tyrosine and tyramine were oxidized to form halogenated catechols such as halogenated L-DOPA and dopamine. In a one-pot synthetic approach, the enzyme oxidation reaction was coupled to the Pictet-Spengler reaction, through the addition of an aldehyde, to generate halogenated THIs. The Pictet-Spengler reaction was catalyzed by the phosphate buffer in the reaction solution. The role ...


Multi-Functional Copper(Ii) Drug Candidates As Potential Anti-Cancer Agents, Tadhg James Patrick Mc Givern Jun 2016

Multi-Functional Copper(Ii) Drug Candidates As Potential Anti-Cancer Agents, Tadhg James Patrick Mc Givern

PhD theses

The development of metal complexes as therapeutic agents remains a focal point of modern medicinal inorganic chemistry. While platinum drugs are well established therapeutic agents, recent progress has shown that some copper complexes possess enhanced cytotoxic activity and in vivo cytotoxic tolerance owing to their DNA binding and DNA scission capabilities. In parallel, the design, synthesis and evaluation of enzyme inhibitors rationally chosen for their potential in suppressing tumour cell proliferation as well as possessing selective toxicity towards tumour over normal cells is another area receiving considerable attention of late.

To date, we have successfully synthesized a library of novel ...


The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger May 2016

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-current

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.


Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying May 2016

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the ...


Assessment Of Purification Methods For The Removal Of Endotoxins From Polymers Generated By E. Coli, Jason R. Pauldine May 2016

Assessment Of Purification Methods For The Removal Of Endotoxins From Polymers Generated By E. Coli, Jason R. Pauldine

Honors Theses

In the medical field, specialty polymers have great potential to meet the demands for bioabsorbable materials as base materials for new technologies. Targeted drug delivery, scaffolds for stem cell growth and intraoperative hemostasis are just a few of the many potential applications for these polymers. Bacterially derived polymers, which are known to be biocompatible, often contain harmful endotoxins. Removal of these endotoxins is necessary to create a safe biocompatible product that meets the FDA requirements on endotoxin limits for implants. This study examines the effectiveness of methanol and sodium hydroxide purification of Clear Coli™ developed by Lucigen and on LSBJ ...


Staphylococcal Nuclease And Ubiquitin Local Folding Energies And Rates Using Peps-Hdx-Esi-Ms, Julie Rhee May 2016

Staphylococcal Nuclease And Ubiquitin Local Folding Energies And Rates Using Peps-Hdx-Esi-Ms, Julie Rhee

Chemistry & Biochemistry Undergraduate Honors Theses

In this study, Protein Equilibrium Population Snapshot Hydrogen-Deuterium Exchange Electrospray Ionization Mass Spectrometry (PEPS-HDX-ESI-MS) was applied to study the local regions of model proteins, staphylococcal nuclease and ubiquitin. The hydrogen deuterium exchange (HDX) has become a key technique for studying the structural and dynamic aspects of proteins in solution. This technique creates a rapid exchange between all of the exchangeable hydrogen ions with deuterium when the protein is exposed to a solvent. The PEPS method is an equilibrium-based method used to determine the populations of the closed native and open denatured states of a protein. By combining the applications of ...


Synthesis Of A Novel Cox-2 Inhibitor Analog For Pet Scan Imaging, Rebecca Neighbor May 2016

Synthesis Of A Novel Cox-2 Inhibitor Analog For Pet Scan Imaging, Rebecca Neighbor

Chancellor’s Honors Program Projects

No abstract provided.


Catalytic Transfer Hydrogenation Of Nitroalkenes To Primary Amines, Brendan Phillips Apr 2016

Catalytic Transfer Hydrogenation Of Nitroalkenes To Primary Amines, Brendan Phillips

Chemistry Honors Papers

This work describes synthetic methodology development in organic chemistry. The goal of this work is to demonstrate new ways of making biologically-relevant molecules that are in line with the principles of green chemistry (chemical practices which seek to be, regarding human and environmental health, benign by design). To this end, a new method has been developed toward the introduction of primary amine functionalities into organic molecules from readily-available aldehydes, via reduction of nitroalkene intermediates. Traditional methods of reducing nitroalkenes to primary amines require harsh conditions, often produce stoichiometric amounts of metal salt waste, and present significant safety challenges to the ...


The Design And Synthesis Of Ghrelin Analogues As Non‐Invasive Ghs‐R1a Imaging Probes, Carlie L. Charlton Feb 2016

The Design And Synthesis Of Ghrelin Analogues As Non‐Invasive Ghs‐R1a Imaging Probes, Carlie L. Charlton

Electronic Thesis and Dissertation Repository

The field of molecular imaging is constantly growing and evolving in order to provide the best possible healthcare for patients in various stages of disease and therapy. Molecular imaging aims to locate specific markers of disease by selectively targeting the markers of interest with high selectivity and visualizing the accumulation using external detection. The growth hormone secretagogue receptor-1a (GHS-R1a) has been shown to be involved in various important biological functions such as energy homeostasis and cardiac contractility. GHS-R1a has shown involvement in proliferation, migration and cell invasion of specific cancer subtypes. Therefore, targeting GHS-R1a is an important marker of different ...


Synthesis Of Novel Aporphine-Inspired Neuroreceptor Ligands, Nirav R. Kapadia Feb 2016

Synthesis Of Novel Aporphine-Inspired Neuroreceptor Ligands, Nirav R. Kapadia

All Dissertations, Theses, and Capstone Projects

Aporphines are a group of tetracyclic alkaloids that belong to the ubiquitous tetrahydroisoquinoline family. The aporphine template is known to be associated with a range of biological activities. Aporphines have been explored as antioxidants, anti-tuberculosis, antimicrobial and anticancer agents. Within the Central Nervous Systems (CNS), aporphine alkaloids are known to possess high affinity for several clinically valuable targets including dopamine receptors (predominantly D1 and D2), serotonin receptors (5-HT1A and 5-HT7) and α adrenergic receptors. Aporphines are also inhibitors of the acetylcholinesterase enzyme – a clinical target for the treatment of Alzheimer’s disease. Considering the diverse profile ...


Mutagenesis-Based Active-Site Characterization Of The Diabetes Drug Target Mitoneet, Lisa Mickley Jan 2016

Mutagenesis-Based Active-Site Characterization Of The Diabetes Drug Target Mitoneet, Lisa Mickley

Williams Honors College, Honors Research Projects

This project investigates the cluster stability of an outer mitochondrial membrane protein mitoNEET under mutational stress and drug binding analysis. MitoNEET is a part of a class of proteins that coordinate an Fe-S molecule into its tertiary structure. This protein is believed to facilitate the oxidative capacity of the electron transport chain by reversible loss of its coordinated Fe-S molecule. The research of this paper uses site directed protein mutagenesis to selectively alter the three cysteine, one histidine cluster coordination into more common coordination patterns such as two cysteine, two histidine or four cysteine. The ultimate goal is to optimize ...


Exploring The Relationship Of Mbd1 Protein Binding Cpg Sites Of Methylated Dna, Shelby L. Scherer Jan 2016

Exploring The Relationship Of Mbd1 Protein Binding Cpg Sites Of Methylated Dna, Shelby L. Scherer

University Honors Program Theses

Methylated DNA binding (MBD) proteins control transcriptional regulation by binding methylated DNA at CpG islands to modulate transcriptional activation and silencing of specific genes such as tumor suppressors. The goal is to explore the structure/function relationship between MBD proteins and methylated DNA recognition. By synthesizing the methylated DNA binding region of the MBD1 protein, binding studies test the peptide’s affinity and specificity for methylated DNA. Fluorescence, circular dichroism, and thermal denaturation techniques are utilized to determine the binding affinities and structures of peptides. Studies of peptide mutations can monitor the effectiveness of methylated DNA binding compared to the ...


The Study Of Nf-Κb Peptide Mimics And How Proteins Bind Dna, Allee M. Murray Jan 2016

The Study Of Nf-Κb Peptide Mimics And How Proteins Bind Dna, Allee M. Murray

University Honors Program Theses

The protein complex nuclear factor kappa B (NF-κB) is widely considered to be one of the most influential transcription factors when studying cellular functions. Peptide mimics of NF-κB aim to inhibit DNA binding in order to displace the natural transcription factor, therefore inhibiting transcription and translation. In theory, NF-κB is not the problem; the real problem lies in directing the synthesis and expression of harmful proteins. In conjunction with this, the project aims to study NF-κB and its structure and function to determine what criteria are important for the binding of DNA in order to design a peptide that comes ...


Towards An Understanding Of Pharmacologically Induced Intracellular Changes In Nicotinic Acetylcholine Receptors: A Fluorescence Microscopy Approach, Ashley M. Loe Jan 2016

Towards An Understanding Of Pharmacologically Induced Intracellular Changes In Nicotinic Acetylcholine Receptors: A Fluorescence Microscopy Approach, Ashley M. Loe

Theses and Dissertations--Chemistry

Upregulation of nicotinic acetylcholine receptors (nAChRs) is a well-documented response to chronic nicotine exposure. Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels consisting of alpha (α2-10) and beta (β2-4) subunits. Nicotine, an agonist of nAChRs, alters trafficking and assembly of some subtypes of nAChRs, leading to an increase in expression of high sensitivity receptors on the plasma membrane. These physiological changes in nAChRs are believed to contribute to nicotine addiction, although the mechanism of these processes has not been resolved. Recently, many studies have converged on the idea that nicotine induces upregulation by an intracellular mechanism. In this dissertation, expression ...