Biochemistry Commons^™

The Basis For Limited Specificity And Mhc Restriction In A T Cell Receptor Interface, Kurt H. Piepenbrink, Sydney J. Blevins, Daniel R. Scott, Brian M. Baker

Department of Biochemistry: Faculty Publications

αβ Tcell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including specificity, crossreactivity and MHC restriction. Here we report a comprehensive thermodynamic deconstruction of the interaction between the A6 TCR and the Tax peptide presented by the class I MHC HLA-A*0201, uncovering the physical basis for the receptor’s recognition properties. Broadly, our findings are in conflict with widely held generalities regarding TCR recognition, such as the relative contributions of central and peripheral peptide residues and the roles of the hypervariable and germline …

Synthesis Of 4-Azidocoumarins And Their Use In Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions, Anthony J. Netsuri

Dissertations and Theses

Triazole-containing compounds have shown great biological activity ranging from antiviral, antibacterial, to anticancer, to name a few. Coumarin derivatives have also shown interesting biological activities. The combination of these bioactive compounds appears to have great promise for new and future medicines. In this work, various 4-azido-coumarins were synthesized via the transformation of the 4-hydroxy derivatives to 4-benzotriazolyloxy coumarins by reaction with the peptide coupling agent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1,8-diazabicycloundec-7-ene (DBU) as the base, in tetrahydrofuran (THF) solvent. The 4-benzotriazolyloxy coumarins were converted to the 4-azidocoumarins by reaction with sodium azide (NaN3), and the overall process was simplified to a …

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O₂^-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …

Understanding Multidrug Resistance In Gram-Negative Bacteria -- A Study Of A Drug Efflux Pump Acrb And A Periplasmic Chaperone Sura, Meng Zhong

Theses and Dissertations--Chemistry

Multiple drug resistance (MDR) has been a severe issue in treatment and recovery from infection.Gram-negative bacteria intrinsically exhibit higher drug tolerance than Gram-positive microbes. In this thesis, two proteins involved in Gram-negative bacterial MDR were studied, AcrB and SurA.

Resistance-nodulation-cell division pump AcrAB-TolC is the major MDR efflux system in Gram-negative bacteria and efficiently extrudes a broad range of substances from the cells. To study subtle conformational changes of AcrB in vivo, a reporter platform was designed. Cysteine pairs were introduced into different regions in the periplasmic domain of the protein, and the extents of disulfide bond formation were …

Determination Of Structural Stabilities Of Metal-Free Porphyrin Cytochrome C, Zinc Cytochrome C, And Cobalt Cytochrome C, Usha K. Tottempudi

Masters Theses

No abstract provided.

Epigenetic Regulation Of Oxysterol Formation, Steve Meaney

Articles

Oxysterols are oxygenated derivatives of cholesterol that may be formed by either enzymatic or non-enzymatic mechanisms. Expression of the genes responsible oxysterol synthesis (GROS) is known to be restricted across different tissues and cell types. Regulation of the transcription of GROS and the activity of their enzyme transcripts has been the subject of intense activity for many years. Recent studies have sought to decipher the mechanism(s) that underpin the restricted expression of the GROS. Available data indicates that epigenetic mechanisms have an important role to play in the control of the expression of GROS. In the current review we summarize …

Expression And Characterization Of The Major Capsid Protein (Mcp) Of A Giant Marine Virus: Cafeteria Roenbergensis Virus, Sayan Chakraborty

Open Access Theses & Dissertations

The oceans play significant roles in maintaining the climate on Earth and providing nutrients to the whole biosphere. Oceanic microbes produce approximately half of the Earth's oxygen. It has been shown that the populations of microbial communities in oceans are largely regulated by viral infection and thus affect the marine ecosystem. Cafeteria roenbergensis Virus (CroV) is a giant marine virus with a linear, double stranded, and AT-rich DNA genome. The genome of CroV has a size of 744kb and encodes for 544 predicted genes. CroV derived its name from its host, a unicellular marine zooplankton Cafeteria roenbergensis (Cro) that is …

Giardia Lamblia: Regulation Of Cyst Production By Glycosphingolipids, Tavis Lyle Mendez

Open Access Theses & Dissertations

The diplomonad protist, Giardia lamblia, colonizes and replicates in the small intestine of mammals. In humans, Giardia infection (known as giardiasis) can be symptomatic or asymptomatic with the former being associated with fatty stool, abdominal pain, malnutrition, and weight loss. Both cell-mediated and humoral immune responses against Giardia infection are possible, and adaptive responses have been reported to be important for controlling the infection. Non-immune components such as secretory immunoglobulin, intestinal lipids, and bile acids also play significant roles in determining the severity of the infection by Giardia.

Giardia exists in two morphologic forms--trophozoites and cysts--and maintains a simple life …

Critical Functions Specified By The Mll Cxxc Domain Determine Leukemogenic Capacity, Noah Warren Birch

Dissertations

TheMixed Lineage Leukemia(MLL) gene can participate in chromosomal translocations which generate a fusion protein leading to acute leukemia. A better understanding of how MLL fusion proteins contribute to leukemia is necessary in order to develop more effective treatments. In my dissertation project, I investigated the functional role of amino acids within the MLL CXXC domain to determine how specific residues contribute to leukemogenic capacity.

MLL fusion proteins retain the amino-terminal portion of MLL including the CXXC DNA-binding domain while the carboxy-terminal portion is comprised of a fusion partner. The closest homolog of MLL, MLL2 (alternatively named MLL4), also contains a …

Biochemical, Structural, And Drug Design Studies Of Multi-Drug Resistant Hiv-1 Therapeutic Targets, Tamaria Grace Dewdney

Wayne State University Dissertations

Protein point mutations acquired as a mechanism of survival against therapeutics cause structural changes that effect protein function and inhibitor binding. This work investigates the structural mechanisms that lead to multi-drug resistance to HIV-1 protease and integrase inhibitors.

Proper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for HIV infection and viral replication. This feature has made HIV-1 protease an attractive target for antiretroviral drug design for the treatment of HIV-1 infected patients, thus the development of drug resistance has arisen as a major therapeutic and drug design challenge. To understand the molecular mechanisms leading to drug resistance we …

Structural Basis For Ternary Complex Formation Between Tau, Hsp90, And Fkbp51, Alexander Steven Barrett

USF Tampa Graduate Theses and Dissertations

The accumulation of the microtubule associated protein tau has been implicated in several neurological disorders; however, its interaction with chaperones along its normal degradation pathway remains largely uncharacterized at single residue resolution. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to probe the interaction between tau, the molecular chaperone Hsp90, and the immunophilin FKBP51. Resonance intensity changes were observed for specific residues in the heteronuclear single quantum coherence (HSQC) spectra of 15N-labeled tau in the presence of Hsp90 and/or FKBP51. Analysis of the HSQC spectra identified the two hydrophobic hexapeptide motifs located at residues V275 - K280 and …

Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and biochemical activities of novel water-soluble β-lactam analogues of combretastatin A-4 are described. The first series of compounds investigated, β-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells. They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells. The second series of compounds, β-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of …

Intercalibraton In Chemical Oceanography-- Getting The Right Number, Gregory A. Cutter

OES Faculty Publications

Intercalibration has a strict metrological definition, but in brief, it's an open sharing of methods and results between laboratories to achieve the most accurate data with the fewest random and systematic errors. In the field of chemical oceanography where concentrations of many constituents can be in the nano- to picomolar range, the salt water matrix can be difficult to analyze, and knowing the exact concentrations, or even chemical forms, of biologically required elements is essential, intercalibration is a very relevant and needed tool. Implementing it is not simple because errors can occur at any step in the process of taking …

Using Ammonium Pore Water Profiles To Assess Stoichiometry Of Deep Remineralization Processes In Methanogenic Continental Margin Sediments, David J. Burdige, Tomoko Komada

OES Faculty Publications

In many continental margin Sediments, a deep reaction zone exists which is separated from remineralization processes near the sediment surface. Here, methane diffuses upward to a depth where it is oxidized by downwardly diffusing sulfate. However, the methane sources that drive this anaerobic oxidation of methane (AOM) in the sulfate-methane transition zone (SMT) may vary among sites. In particular, these sources can be thought of as either (i) "internal" sources from in situ methanogenesis (regardless of where it occurs in the sediment column) that are ultimately coupled to organic matter deposition and burial, or (ii) "external" sources such as hydrocarbon …

Malnutrition In Sickle Cell Anemia: Implications For Infection, Growth And Maturation, Hyacinth I. Hyacinth, Oluwatoyosi A. Adekeye, Christopher S. Yilgwan

Journal of Social, Behavioral, and Health Sciences

Sickle cell anemia (SCA) is a genetic disease that affects mostly individuals of African and/or Hispanic descent, with the majority of cases in sub-Saharan Africa. Individuals with this disease show slowed growth, delayed sexual maturity, and poor immunologic function. These complications could partly be explained by the state of undernutrition associated with the disease. Proposed mechanism of undernutrition include protein hypermetabolism, decreased dietary intake possibly from interleukin-6-related appetite suppression, increased cardiac energy demand/expenditure, and increased red cell turnover. All the above mechanisms manifest as increased resting energy expenditure. Nutritional intervention utilizing single or multiple nutrient supplementation has led to improved …

Distributions Of Particulate Heme B In The Atlantic And Southern Oceans- Implications For Electron Transport In Phytoplankton, Martha Gledhill, Eric P. Achterberg, David J. Honey, Maria C. Nielsdottir, Micha J.A. Rijkenberg

OES Faculty Publications

Concentrations of heme b, the iron-containing component of b-type hemoproteins, ranged from b concentrations were enhanced in the photic zone and decreased with depth. Heme b concentrations correlated positively with chlorophyll a (chl a) in the TNA (r=0.41, pb did not correlate with chl a in the IB or SS. In the IB and SS, stations with high-chlorophyll and low-nutrient (Fe and/or Si) concentrations exhibited low heme bconcentrations relative to particulate organic carbon (< 0.1 μmolmol^-1, and high chl a:heme b ratios (> 500). High chl a:heme b ratios resulted from relative decreases in …

Plant-Pathogen Interactions Associated With Wasting Disease In The Tropical Seagrass Thalassia Testudinum., Kyle Loucks

UNF Graduate Theses and Dissertations

Lipopolysaccharide (LPS) was shown to serve as a strong elicitor of the early defense response in the subtropical seagrass Thalassia testudinum Banks ex König and was capable of inducing an oxidative burst identified at the single cell level. The formation of reactive oxygen species (ROS) included a diphenylene iodonium sensitive response, suggesting the involvement of an NADPH oxidase. A 900 bp fragment of this enzyme was sequenced and found to encode a NAD binding pocket domain with extensive homology to the Arabidopsis thaliana rbohF (respiratory burst oxidase homolog) gene. Pharmacological dissection of the early events preceding ROS emission revealed that …

Bacteriostatic Effects Of Sucralose On Environmental Bacteria, Arthur Phillip Omran Jr.

UNF Graduate Theses and Dissertations

Sucralose is a zero calorie sweetener developed and manufactured by Tate and Lyle Sweetener Company in the 1980’s. They sell the sweetener compounded with maltodextrin and dextrose under the brand name Splenda®. Sucralose was developed as a low cost artificial sweetener that is non-metabolizable in humans and can withstand changes in pH and temperature. It is not degraded by the waste water treatment process. Since the molecule can withstand heat, acidification and microbial degradation it is accumulating in the environment, and has been found in waste water, estuaries, rivers and the Gulf Stream. The highest concentration of environmental sucralose detected …

Sequencing A Dna Polymerase Alpha Gene In Thermomyces Lanuginosus, Sonia Tien-Yang Han

Honors Program Theses

DNA polymerases are present in all living organisms and it is expected that there should be a reasonable degree of conservation, or similarity in how the polymerases function, between species. This makes the possibility of developing treatments using DNA polymerase more likely, as the treatment would not necessarily depend on using human DNA as the base material, which would be more expensive. However, this cannot be known unless there is a reasonable number of DNA sequences available from multiple species to analyze. This is a growing research, but the majority of sequences known are from mammals. Currently there is very …

Expressed Sequence Tag For Dna Polymerase Alpha In Embryonic Chicken Brain, Rebecca Krewer

Honors Program Theses

Replicative DNA polymerases are enzymes located in the nuclei of cells. They have a role in the control of DNA synthesis in all cells, and problems with their function and control affect cell growth. One of these polymerases, DNA polymerase alpha ("pol α"), is a possible point of control for cell growth because it initiates DNA synthesis. The ability to selectively turn on or shut off this polymerase in cells could provide answers to problems ranging from cancer's unregulated growth to regeneration of tissues. However, control mechanisms for DNA pol α are not fully understood at this time. The central …