Physical Sciences and Mathematics Commons^™

Determining The Relative Activities Of Wild-Type Mycobacterium Tuberculosis Indole-3-Glycerol Phosphate Synthase And Mutants E57a And E219a With An Investigation Into The Relationship Between Wild-Type Mycobacterium Tuberculosis Igps Activity And Ph, Thomas Emmanuel Candela

Theses, Dissertations and Culminating Projects

The relationship between wild-type protein indole-3-glycerol phosphate synthase (IGPS) activity and pH was investigated through the formation of pH activity profiles, and the relative catalytic activities of wild-type Mycobacterium tuberculosis and mutants E57A and E219A were also deduced in this work. The activity of each enzyme variant was determined by reacting native substrate 1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate with enzyme buffered at pH 7.5 in a cuvette and using a fluorometer to detect the increase in fluorescent signal produced by the formation of fluorescent product indole-3 glycerol phosphate. Work with wild-type IGPS showed the enzyme to have a kcat of 1.26 ± 1.75 (s …

Characterizing Functions Of Two Regulatory Proteins In The Parasitic Nematode Brugia Malayi And Their Potential As Drug Targets In Treating Lymphatic Filariasis, Brittany Amber Hart

Theses, Dissertations and Culminating Projects

Lymphatic filariasis (LF) is a debilitating disease caused by parasitic nematodes that affect millions of people in largely tropical environments. While drugs are available for treating LF, they suffer from a lack of efficacy against adult parasites, toxicity, and emergence of resistance. Here, we describe two novel potential drug targets within the filarial parasite, Brugia malayi (B. malayi). These two proteins, bm9350, a predictive MAPK stress response protein, and bm2032, a potential histone modifying enzyme, have little or no annotation or experimental evidence of function. Using predictive analysis and tools, we examined potential functions of these proteins and their potential …

Studies Toward The Synthesis Of A Novel Diamine Scaffold, Joseph Edward Quinlan Iii

Theses, Dissertations and Culminating Projects

The orexin system in humans contains receptors Orexin 1 (OX1) and Orexin 2 (OX2). These receptors are involved in numerous physiological processes including wake/sleep cycling, energy homeostasis, and motivation/reward. In scientific literature, it is known that antagonism of these receptors exhibits therapeutic effects in the realm of cocaine and alcohol addiction, as well as sleep disorders. On the market today exist drugs for treatment of sleep disorders through orexin receptor antagonization. Here we report a synthesis toward novel conformationally rigid antagonists of the orexin receptor system that may provide improved affinity and/or selectivity compared to known compounds. We report the …

Discovery Of Single-Stranded Dna Aptamers For The Detection Of Ranavirus, Allyssa Angel

Theses, Dissertations and Culminating Projects

A key problem when developing molecular diagnostic techniques is procuring target detection probes. The need of a stable and selective probe is necessary for accurate target identification in disease detection. Antibodies are widely used but they are unstable at ambient temperatures and are expensive and time consuming to develop. The use of aptamers (short singlestranded DNA) as molecular probes provides several advantages over protein-based methods because they are more stable, easily selected and modifiable. The need of a reliable and stable probe is necessary for accurate detection tests in the field for disease monitoring. Currently, field methods are limited in …

Synthesis Of Amide And Sulfonamides As Pde11 Inhibitors, Noor Abouchakra

Theses, Dissertations and Culminating Projects

With increasing age, individuals begin to experience cognitive decline, especially memory deficits. Given the lack of effective treatments for memory loss, a new promising approach includes targeting second messenger systems that play a critical role in cognitive processes by inhibiting phosphodiesterases (PDEs), specifically PDE11A since its expression is restricted to the brain. PDE11A is responsible for regulating levels of second messengers, such as cyclic AMP and cyclic GMP, which participate in several biochemical processes relating to long term memory function. Since these signaling cascades are controlled by PDEs that result in turning off the signaling pathway, inhibiting phosphodiesterases will lead …

A Study And Synthesis : Bronze Compounds, Patricia Rose Olsen

Theses, Dissertations and Culminating Projects

The focus of this thesis is the investigation of ternary and quaternary reduced metal oxide compounds termed “bronzes.” The name bronze originally arose from the metallic-like luster of these compounds. Examples of these compounds range from sodium tungsten oxides to the more complex potassium cesium molybdenum oxides. These compounds are crystalline solids at room temperature.

The “bronzes” are compounds that have been studied since their initial synthesis by Wohler in 1824. These compounds belong to a class of compounds that are known as “nonstoichiometric” compounds. The general formula for reduced ternary transition metal oxides is AxMyOz. In this general formula, …

A Comparative Study Of Drug Affinities Determined By Thermofluor And Kinetic Analysis, Oruba Shatnawi

Theses, Dissertations and Culminating Projects

Determining the binding affinity and potency in vitro is one of the significant steps that can give a clue for a new candidate drug during the drug discovery process. Thermofluor is a method used in measuring binding affinity (Kd) of protein-ligands interaction through determining the change in thermal denaturation temperature of protein using real time PCR (RT-PCR). Kinetic analysis assay is used to screen a library of compounds to calculate their potencies (IC50) and inhibition constants (Ki) and it can be performed by spectrophotometer technique. In this study, we used bovine carbonic anhydrase II (BCA II) enzyme, and four of …

Preparation And Crystal Structures Of Racemic And Quasiracemic Imidazole Or N-Methyl Imidazole Copper Complexes Containing Substituted N-Benzoylalanines, Emily Catherine Chong

Theses, Dissertations and Culminating Projects

A quasiracemate is the cocrystallization of two similarly shaped but chemically distinct molecules of opposite handedness. There has been limited to no work regarding quasiracemates in the field of inorganic chemistry. The goal of this study was to prepare various metal based enantiomers, racemates, and quasiracemates using N-benzoylalanines with imidazole or N-methylimidazole as ligands bound to copper to form a metal complex. In this study, we developed a method to prepare substituted N-benzoylalanines and its copper complexes. We also prepared one co-crystal between two differently substituted N-benzoylalanines.

This work reports the successful synthesis and crystal structure analysis of an organic …