Inorganic Chemicals Commons^™

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Exploiting The Heavy Chain Glycans For The Improvement Of Radioimmunoconjugates, Cindy Rodriguez

Dissertations, Theses, and Capstone Projects

Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. A handful of recent preclinical studies suggest that binding by FcR and particularly FcyRI can affect the pharmacokinetic profiles of 89Zr-labeled radioimmunoconjugates. Fc receptors (FcR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcRs affect the in vivo performance of radiolabeled antibodies. Antibodies …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Determination Of The Effects Of Added Methionine On The Toxicity Of Platinum Drugs In Saccharomyces Cerevisiae, Kassidy Owens, Jonathan White

Longwood Senior Thesis Proposal

Platinum (Pt) drugs are used in about half of all anticancer treatments. A common way to study Pt drugs is by using S. cerevisiae (brewer’s yeast) as a model cellular organism. One of the most commonly-used strains of yeast is BY4741, which is auxotrophic for (cannot synthesize) several small-molecule nutrients, including the amino acid methionine. Therefore, methionine must be supplemented in the cell culture medium. Interestingly, it is known that methionine can react with Pt compounds, including Pt drugs. Methionine-supplemented media continues to be used to study Pt drugs in yeast, especially BY4741, yet the potential for methionine to interfere …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Leaving Ligand Effects On Reactivity And Solubility Of Monofunctional Platinum(Ii) Anticancer Complexes, Heidi Linn Hruska Millay

Masters Theses & Specialist Projects

Monofunctional platinum(II) complexes, such as phenanthriplatin and pyriplatin, have notably different characteristics from the bifunctional anticancer complexes, such as cisplatin and oxaliplatin, which have detrimental toxicities and resistance associated with them. The unique properties of the monofunctional complexes may be exploited to target cancer cells without producing the toxic side effects associated with the current FDA-approved platinum-based anticancer drugs. To advance the understanding of these monofunctional platinum(II) complexes, this study replaced the chloride leaving ligand with an acetate group, which should increase solubility and alter the rate of reactivity with key amino acid and nucleotide targets. Phenanthriplatin and pyriplatin compounds …

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 metals were not inhibiting IAPP …

Sds Non-Acrylamide Polymeric Gel-Filled Capillary Electrophoresis For Molecular Size Separation Of Protein, Devon Andres

Honors Theses

Sodium dodecyl sulfide (SDS) non-acrylamide gel-filled capillary columns are a new technology being used for analysis and separation of biotechnology-derived proteins. This research was to compare this new technology to the current methods of SDS polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance size-exclusion chromatography (HPSEC). The molecular mass of four different recombinant proteins were determined by two commercialized SDS non-acrylamide gel-filled capillary columns, SDS-PAGE, and HPSEC. The data obtained showed that the SDS non-acrylamide gel-filled capillary columns were compatible with the SDS-PAGE technique for molecular mass determination. HPSEC was shown to be unreliable for molecular weight determination. SDS non-acrylamide gel-filled capillary …