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Articles 1 - 30 of 101
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Kinase-Catalyzed Labeling To Identify Kinase-Substrate Pairs Using Γ-Phosphate Modified Atp Analogs, Rachel Beltman
Kinase-Catalyzed Labeling To Identify Kinase-Substrate Pairs Using Γ-Phosphate Modified Atp Analogs, Rachel Beltman
Wayne State University Dissertations
Post-translational modifications (PTMs) are responsible for a variety of cellular processes. One such PTM is protein phosphorylation, which is catalyzed by kinases. Kinase enzymes play important roles in cellular signaling pathways, but dysregulation of kinase-mediated events results in the formation of diseases, which make kinases favorable drug targets. To uncover the role kinases play in the development of diseases, kinase-mediated cellular events need to be better understood. The current gap in the field is the lack of tools available to identify the kinase that is responsible for specific phosphorylation events within the cell. To improve the gap in the field, …
Extending Plasma Proteome Coverage To Enable Biomarker Discovery, Jordan Bruce Burton
Extending Plasma Proteome Coverage To Enable Biomarker Discovery, Jordan Bruce Burton
Wayne State University Dissertations
Two features make plasma a valued source of health information: First, plasma contains secreted proteins from all tissues in the body and can, therefore, provide information about the health status of all tissues. Second, plasma is available in large quantity using a minimally invasive procedure that is well tolerated. The status of plasma as a valued source of health information is matched by the difficulty in extracting proteome information from the samples. Using state of the art instrumentation a standard analysis of plasma yields quantitative information on approximately 300 proteins. Extreme fractionation strategies coupled with increased mass spectrometry time extends …
Characterizing The Post-Translational Modifications Of The Pro-Oncogenic Type Ii Transmembrane Serine Protease Tmprss13, Carly Elizabeth Martin
Characterizing The Post-Translational Modifications Of The Pro-Oncogenic Type Ii Transmembrane Serine Protease Tmprss13, Carly Elizabeth Martin
Wayne State University Dissertations
TMPRSS13, a type II transmembrane serine protease discovered at the turn of the century, has recently been shown to be significantly overexpressed in both breast cancer (BCa) and colorectal cancer (CRC), and to mediate chemoresistance in cell lines from both cancer types. Furthermore, loss of TMPRSS13 in a genetic model of mouse mammary carcinoma significantly reduced tumor burden and growth rate, and increased overall tumor-free survival. Its location on the cell surface as well as its low expression in normal breast and colon make TMPRSS13 an attractive candidate as an oncogenic biomarker and therapeutic target in cancer. However, little is …
Substrate Profiling Of The Epigenetic Erasers Hdac1 And Lsd1, Herath Mudiyansela Gedara Kavinda Eranga Herath
Substrate Profiling Of The Epigenetic Erasers Hdac1 And Lsd1, Herath Mudiyansela Gedara Kavinda Eranga Herath
Wayne State University Dissertations
Regulators of chromatin structure have emerged as a key driver of transcriptional responses inside the cell. Two such groups of regulators, histone writers and erasers; the proteins, that add or remove histone post translational modifications (PTMs), have become the central players in chromatin structure. Thus, the aberrant expression of writers and erasures is a hallmark in human diseases. For example, overexpression of the erasures histone deacetylase1 (HDAC1) and lysine specific demethylase1 (LSD1) had been reported in many cancers. Currently, HDAC inhibitors have been used successfully for cancer treatment and several inhibitors targeting LSD1 are in clinical trial. To date, apart …
An In Vivo Inducible Expression System To Determine Antibacterial Activity Of Peptides, Rabiul Islam
An In Vivo Inducible Expression System To Determine Antibacterial Activity Of Peptides, Rabiul Islam
Wayne State University Dissertations
The threat of bacterial resistance throughout the world has created tremendous challenges to clinicians. Some bacterial species have acquired resistance to not only single antibiotics, but also to multiple compounds, which is called multidrug resistance. Since the early discovery of resistance to penicillin, scientists have been developing new drugs to combat antibiotic resistance. In some cases, it took less than a decade to develop resistance to a new antibiotic. The World Health Organization (WHO) reported several deadly multi-drug-resistant bacteria, some of which cause life-threating illnesses. Each year more than 35,000 people in the United States die from antibiotic-resistant bacterial infections. …
Mnrr1: Understanding The Role Of A Novel Mitochondrial-Nuclear Regulator, Stephanie L. Gladyck
Mnrr1: Understanding The Role Of A Novel Mitochondrial-Nuclear Regulator, Stephanie L. Gladyck
Wayne State University Dissertations
Mitochondria are complex organelles that generate most of the energy required to sustain life and function in metabolic and signaling pathways required to maintain cellular homeostasis. MNRR1 (mitochondrial nuclear retrograde regulator 1 or CHCHD2) is a small, bi-organellar twin CX9C protein that is emerging as an important regulator of mitochondrial function, apoptosis, and cellular stress by participating in mitochondrial-nuclear crosstalk. Our lab has previously shown that in the mitochondria, MNRR1 regulates complex IV (Cytochrome c oxidase or COX) and is able to finetune the oxidase function through phosphorylation status. We have also shown that during stress, mitochondrial MNRR1 levels deplete, …
Developing Inhibitors Of Uchl5 Deubiquitinase In The Proteasome, Harshani Sewvandi Gurusingha Arachchige
Developing Inhibitors Of Uchl5 Deubiquitinase In The Proteasome, Harshani Sewvandi Gurusingha Arachchige
Wayne State University Dissertations
Ubiquitin proteasomal system (UPS) plays a vital role in maintaining protein homeostasis by eliminating misfolded and damaged proteins in a eukaryotic cell. Target proteins to be degraded are modified by poly-ubiquitination, which leads to degradation by 26S proteasome. Before entering the 20S catalytic subunit, the 19S regulatory particle is responsible for binding, unfolding, and deubiquitinating the target protein. Based on the nature of the polyubiquitin tag, removal of the ubiquitin is performed by the deubiquitinases (DUBs) associated with the proteasome.Ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5) is one of the three DUBs in the proteasome. UCHL5 regulates many cellular functions and …
Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous
Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous
Wayne State University Dissertations
Colorectal cancer (CRC) constitutes a major burden on the healthcare system as the second most commonly diagnosed cancer in the developed world. Dietary folate is considered an important modulator of colorectal cancer. Folate restriction has been implicated in increasing CRC incidence by disrupting nucleotide synthesis, Impacting DNA methylation and inducing genetic instability. Our research shows that the timing and duration of dietary folate restriction can differentially impact Colorectal cancer initiation. Acclimating mice to folate restriction for 8 weeks results in a reduced number of preneoplastic lesions compared to mice placed of folate restriction for 1 week prior to initiating the …
Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday
Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday
Wayne State University Dissertations
Oxidative stress and endothelial dysfunction are reported in the cardiovascular and neurovascular diseases. Oxidative stress is caused due to an increase in the generation of reactive oxygen (ROS) and nitrogen species (RNS) and incapacity of antioxidant systems to eliminate ROS and RNS. Endothelial dysfunction is characterized by a reduction in nitric oxide (NO) bioavailability. NO is constitutively produced by enzyme endothelial nitric oxide synthase (eNOS). A reduction in tetrahydrobiopterin (BH4), which is an essential cofactor of eNOS, can lead to eNOS uncoupling. There is complex interplay between the ROS/RNS and antioxidant system underlying pathophysiologies of vascular diseases, however our quantitative …
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Wayne State University Dissertations
Rat1 is a 5′→3′ exoribonuclease in budding yeast belonging to the XRN-family of nucleases. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its homolog in metazoan have been shown to function in multiple facets of RNA metabolism. In this study, we report a novel role of Rat1 in splicing of pre-mRNA in budding yeast. In the absence of the functional Rat1 in the nucleus, an increase in the level of unspliced transcripts was observed in yeast cells. Strand-specific TRO analysis revealed that the accumulation of unspliced transcripts upon …
Use Of Alkoxyamines To Quantify And Map Uracils And To Kill B Cell Cancers, Madusha Lakshani Watuthanthrige Perera
Use Of Alkoxyamines To Quantify And Map Uracils And To Kill B Cell Cancers, Madusha Lakshani Watuthanthrige Perera
Wayne State University Dissertations
Majority of B-cell lymphoma and leukemia originates in germinal centers and over express AID resulting high levels of uracils and eventually AP sites. Treating cells with a small alkoxyamine AA3 with a terminal alkyne group specifically killed B cell lymphoma cell lines without killing normal human B cells and non-hematological cancers. To study the cytotoxicity of AA3, I designed and synthesized a series of AA3 analogs with and without the alkyne group. Using cytotoxicity assays I demonstrated that the alkyne functionality plays a major role in AA3 cytotoxicity in B-cell cancers and further showed that the effectiveness is modulated by …
Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage
Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage
Wayne State University Dissertations
Post translational modifications regulate a variety of biological processes inside the cell.Protein phosphorylation is one such PTM modification catalyzed by protein kinases, which aid to transfer a signal from one place to another inside the cell. However, irregularities in kinase-mediated signaling are often implicated in many diseases, making kinases effective drug targets. To understand kinase-related disease formation and to discover drugs to treat these diseases, it is crucial to have a clear understanding on kinase-mediated cell signaling networks. A current gap in the kinase biology field is a lack of tools to identify which kinase phosphorylates which protein substrate inside …
Variations On A Theme: Intricacies Of Unanchored Poly-Ubiquitin Signaling And Toxicity, Jessica Renee Blount-Pacheco
Variations On A Theme: Intricacies Of Unanchored Poly-Ubiquitin Signaling And Toxicity, Jessica Renee Blount-Pacheco
Wayne State University Dissertations
Ubiquitin is an 8.5 kDa post-translational modifier involved in essentially all eukaryotic cellular processes. Through a process called ubiquitination, ubiquitinating enzymes chemically attach ubiquitin to substrate proteins to control their fates, resulting in anything from their recruitment into signaling pathways to their proteasomal degradation, with a plethora of possibilities in between. Ubiquitin molecules can also be attached to one another, resulting in poly-ubiquitin chains with various effects depending on the number of ubiquitin molecules and the specific amino acid residues used to link them together. While most poly-ubiquitin in the cell exists as conjugated species, there are also untethered poly-ubiquitin …
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Wayne State University Dissertations
With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate-linked cisplatin analog, cis-dichlorido[(2-β-D-glucopyranosidyl)propane-1,3-diammine]platinum (5) has been studied. The aim was to evaluate …
Biochemical, Structural, And Drug Design Studies Of Aspartate Transcarbamoylase From Pseudomonas Aeruginosa And Staphylococcus Aureus, Chandni Patel
Biochemical, Structural, And Drug Design Studies Of Aspartate Transcarbamoylase From Pseudomonas Aeruginosa And Staphylococcus Aureus, Chandni Patel
Wayne State University Dissertations
Sepsis affects 1.7 million people in the United States every year and nearly 270,000 people die as a result. Sepsis is characterized by systemic inflammation from an infection leading to organ dysfunction and death. Multi-drug resistance in bacteria is increasing globally, and Pseudomonas aeruginosa and Staphylococcus aureus are notorious for their multi-drug resistance and pose a serious need for the development of new antibiotics. The levels of pyrimidines in blood are too low to sustain the growth of bacteria, so they must rely on pyrimidine biosynthesis. Previous studies have shown that a defect in several pyrimidine biosynthetic enzymes resulted in …
Predicting The Structure And Selectivity Of Coiled-Coil Proteins, Mojtaba Jokar
Predicting The Structure And Selectivity Of Coiled-Coil Proteins, Mojtaba Jokar
Wayne State University Dissertations
A coiled-coil protein structure consists of two (in coiled-coil dimers) or more interacting α-helical strands that together form a left-handed supercoil structure. Many coiled-coil proteins are involved in significant biological functions such as the regulation of gene expression, known as transcription factors. Also coiled-coil structures entail unique mechanical properties critical to the function and integrity of various motor proteins, cytoskeletal filaments and extra-cellular matrix proteins. Engineering these transcription factors is also expected to create more efficient and practical solutions to treat neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion …
The Dynamic Nature And Biophysical Characterization Of Isu1, Fe-S Cluster Assembly Scaffold Protein In Saccharomyces Cerevisiae, And Its Significance To Human Disease, Brianne Elizabeth Lewis
The Dynamic Nature And Biophysical Characterization Of Isu1, Fe-S Cluster Assembly Scaffold Protein In Saccharomyces Cerevisiae, And Its Significance To Human Disease, Brianne Elizabeth Lewis
Wayne State University Dissertations
Mitochondrial Fe-S cluster biosynthesis is accomplished within yeast utilizing the biophysical characteristics of the “Isu1” scaffold protein. As a member of a highly homologous protein family, Isu1 has sequence conservation with orthologs and a conserved ability to assemble [2Fe-2S] clusters. Regardless of species, scaffold orthologs can exist in both “disordered” and “structured” conformations and is directly related to conformations utilized during Fe-cofactor assembly. During assembly, the scaffold directs the delivery and the utilization of both Fe(II) and sulfide substrates in order to produce [2Fe-2S] clusters, however Zn(II) binding can alter the activity of the scaffold with stabilizing the protein in …
Role Of Dyslipidemia On Lipid Metabolism In Maintenance Hemodialysis Patients, Eno Latifi
Role Of Dyslipidemia On Lipid Metabolism In Maintenance Hemodialysis Patients, Eno Latifi
Wayne State University Dissertations
Maintenance hemodialysis (MHD) patients experience various abnormalities such as systemic inflammation (SI), oxidative stress (OS), and dyslipidemia (D). Defined as an imbalance of plasma lipids, lipoproteins, and lipid metabolism enzymes, D has been associated with a rise in morbidity and mortality within ESRD patients due to cardiovascular disease (CVD). However, the contribution of each of these parameters to D is poorly understood; moreover, the impact of the following parameters on dyslipidemia in different ethnicities is unknown. Hence, the objective of this study was to characterize D in a multi-ethnic cohort of ESRD patients. We hypothesized that the degree of dyslipidemia …
Trna Aminoacylation: New Protein Players And New Reactions, Whitney Noel Wood
Trna Aminoacylation: New Protein Players And New Reactions, Whitney Noel Wood
Wayne State University Dissertations
TRNA AMINOACYLATION: NEW PROTEIN PLAYERS AND NEW REACTIONS
by
WHITNEY N. WOOD
May 2019
Advisor: Dr. Tamara L. Hendrickson
Major: Chemistry (Biochemistry)
Degree: Doctor of Philosophy
Protein translation must usually occur with high accuracy for an organism to survive. However, Helicobacter pylori, Staphylococcus aureus, and many other microorganisms including important human pathogens, lack one or more aminoacyl-tRNA synthetase (aaRS), the enzymes that typically aminoacylate tRNAs for ribosomal translation. These organisms must use an indirect pathway to aminoacylate some tRNAs. Specifically, H. pylori lacks the genes that encode for asparaginyl- and glutaminyl-tRNA synthetases (AsnRS and GlnRS, respectively). Instead, H. pylori uses …
Perturbation Of Energy Metabolism At The Center Of The Mechanism Of Action Of Valproate, Michael Ghassan Salsaa
Perturbation Of Energy Metabolism At The Center Of The Mechanism Of Action Of Valproate, Michael Ghassan Salsaa
Wayne State University Dissertations
Bipolar disorder (BD) is a common and debilitating psychiatric disorder. Valproic acid (VPA) is one of the major drugs used to treat BD patients. However, it is not universally effective and, in addition, causes severe side effects. Its mechanism of action is not known, which complicates efforts to develop more effective drugs. Studies have established that VPA perturbs metabolism, which is implicated in both the therapeutic mechanism of action of the drug as well as drug toxicity. However, the mechanism whereby VPA causes these perturbations is not understood. To address this knowledge gap, I investigated the acute and chronic effects …
Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake
Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake
Wayne State University Dissertations
Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …
Investigation Of The In Vivo Activity Of Ribosome-Targeting Peptides And Aminoglycosides In Escherichia Coli, Nisansala Sarangi Thilakarathne Muthunayake
Investigation Of The In Vivo Activity Of Ribosome-Targeting Peptides And Aminoglycosides In Escherichia Coli, Nisansala Sarangi Thilakarathne Muthunayake
Wayne State University Dissertations
The development of short peptides that specifically bind to higher-order structures of ribosomal RNA is one promising way to address the problem of antibiotic resistance. However, the poor correlation between in vitro and in vivo activities of these peptides is one of the major questions in antibiotic peptide research. Therefore, one of the main objectives of this dissertation work was to utilize a plasmid-based system to in vivo express ribosome-targeting peptides and study their direct inhibitory effects on bacteria. A specific plasmid system was optimized to in vivo express oncocin, a prolin-rich antimicrobial peptide and its variants in bacteria. Our …
Functional Study Of Smyd2 Glutathionylation In Cardiomyocytes, Dhanushka Nalin Perera Munkanatta Godage
Functional Study Of Smyd2 Glutathionylation In Cardiomyocytes, Dhanushka Nalin Perera Munkanatta Godage
Wayne State University Dissertations
Reactive oxygen species (ROS) are important signaling molecules that contribute to the etiology of multiple muscle-related diseases, including cardiomyopathy and heart failure. There is emerging evidence that cellular stress can lead to destabilization of sarcomeres, the contractile unit of muscle. However, it is not completely understood how cellular stress or ROS induce structural destabilization of sarcomeres or myofibrils. Protein glutathionylation is one of the major protein cysteine oxidative modifications that play an important role in redox signaling and oxidative stress. In this report, we used a clickable glutathione approach in a cardiomyocyte cell line, and found that SET and MYND …
Biochemical And Cellular Studies Of Apobec3 Family Dna-Cytosine Deaminases, Sachini Umedi Siriwardena
Biochemical And Cellular Studies Of Apobec3 Family Dna-Cytosine Deaminases, Sachini Umedi Siriwardena
Wayne State University Dissertations
The AID/APOBEC family of enzymes deaminate cytosines in single-stranded DNA to uracils leading to base substitutions and strand breaks. Members of APOBEC3 family in humans are induced by cytokines produced during the body's inflammatory response to infections and provide innate immunity against viruses. However, there is emerging consensus that these enzymes can cause mutations in the cellular genome depending on the physiological state of the cell and the phase of the cell cycle they are expressed. Since aberrant expression of APOBEC3B was recently identified as a possible source of cancer, we initiated a study to determine the maximally active catalytic …
Alternative Strategies To Inhibit Lysine Methyltransferases And Deubiquitinases In Human Cancers, Nicholas Spellmon
Alternative Strategies To Inhibit Lysine Methyltransferases And Deubiquitinases In Human Cancers, Nicholas Spellmon
Wayne State University Dissertations
X-ray crystallography is the gold standard method for imagining macromolecules to atomic resolution. Three dimensional data is central to understanding the molecular mechanism how DNA, RNA and proteins function in biological events. Structural insights into these events provide a molecular window to visualize how biological molecules influence human health. Visualizing the architecture of these molecules set the stage for rational and selective drug design. The following dissertation utilizes biochemical and biophysical tools, including X-ray crystallography, to shed light on poorly understood mechanisms related to SMYD2 activity and regulation, USP10 architecture and function, and PDZ-RhoGEF dimerization. SMYD2 is one member of …
Investigation Of The Saccharomyces Cerevisiae Gpi Transamidase: Insights Into Its Activity And Subunit-Subunit Interactions, Travis Ness
Wayne State University Dissertations
Glycosylphosphatidylinositol (GPI) anchoring of proteins is a eukaryotic, posttranslational
modification catalyzed by GPI transamidase (GPI-T). The Saccharomyces
cerevisiae GPI-T is composed of five membrane-bound subunits: Gaa1, Gpi8, Gpi16,
Gpi17, and Gab1. Structural and functional studies have been hindered by the
complexity of this enzyme. Conditions to purify the Gpi8:Gaa1:Gpi16 GPI-T heterotrimer
from yeast have been reported, but an understanding of the subunit functions,
interactions, and stoichiometry remain unclear. Furthermore, a reliable, quantitative, in
vitro assay for this important post-translational modification has remained elusive for
nearly three decades.
Our laboratory has developed an in vitro peptide cleavage assay that correlates
changes …
Methionine Sulfoximine: A Novel Anti Inflammatory Agent, Tyler Peters
Methionine Sulfoximine: A Novel Anti Inflammatory Agent, Tyler Peters
Wayne State University Dissertations
ABSTRACT
METHIONINE SULFOXIMINE: A NOVEL ANTI-INFLAMMATORY AGENT
by
TYLER J. PETERS
October 2018
Advisor: William Brusilow
Major: Biochemistry and Molecular Biology
Degree: Doctor of Philosophy
The glutamine synthetase inhibitor methionine sulfoximine (MSO), shown previously to prevent death caused by an inflammatory liver response in mice, was tested on in vitro production of cytokines by mouse peritoneal macrophages triggered with lipopolysaccharide (LPS). MSO significantly reduced the production of Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFα) at 4 and 6 hours after LPS-treatment. This reduction did not result from decreased transcription of IL-6 and TNFα genes, and therefore appeared to …
Carbohydrate-Based Inducers Of Cellular Stress For Targeting Cancer Cell Metabolism, Fidelis Ndombera
Carbohydrate-Based Inducers Of Cellular Stress For Targeting Cancer Cell Metabolism, Fidelis Ndombera
Wayne State University Dissertations
ABSTRACT
CARBOHYDRATE-BASED INDUCERS OF CELLULAR STRESS FOR TARGETING CANCER CELL METABOLISM
by
FIDELIS TOLOYI NDOMBERA
May 2018
Advisor: Dr. Young-Hoon Ahn
Major: Chemistry (Biochemistry)
Degree: Doctor of Philosophy
Metabolic reprogramming and redox control of cancer cells is vital for their proliferation, but also provides selective strategies for treating cancer. Increased generation of reactive oxygen species (ROS) and an intricate control of redox status in cancer cells relative to normal cells provide a basis for designing ROS-inducing anticancer agents. In my work, I designed, synthesized and evaluated carbohydrate-based small molecules for ROS-generation, cytotoxicity and redox signaling and stress response. Our data …
Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth
Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth
Wayne State University Dissertations
Cooperative reactivity of bimettalics can be is observed in many different areas of chemistry and have been increasingly investigated because of the advantageous reactivity when compared to the corresponding mononuclear systems. The focus of my dissertation is on (1) investigation of the homobimetallic cooperativity in lactide polymerization catalysis; (2) investigation of the heterobimetallic cooperativity in the biomimetic studies of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme in order to make a functional model of its active site.
Three new main group bis(alkoxide) complexes Mg(OR)2(THF)2, Zn(Cl)(μ2-OR)2Li(THF) and In(OR)2(μ2-Cl)2Li(THF)2 featuring bulky alkoxide [OCtBu2Ph] were synthesized serve as metal alkoxide precursors for bimetallic lactide …
The Development Of Chemical Methods To Discover Kinase Substrates And Map Cell Signaling With Gamma-Modified Atp Analog-Dependent Kinase-Catalyzed Phosphorylation, Dissanayaka Mudiyanselage Maheeka Madhubashini Embogama
The Development Of Chemical Methods To Discover Kinase Substrates And Map Cell Signaling With Gamma-Modified Atp Analog-Dependent Kinase-Catalyzed Phosphorylation, Dissanayaka Mudiyanselage Maheeka Madhubashini Embogama
Wayne State University Dissertations
Kinase-catalyzed phosphorylation plays an important role in cell physiology by regulating a myriad of cellular functions. Thus aberrant kinase activity is implicated in various diseases. Methods are needed to discover kinase substrates and map signaling pathways to explore biology and to help drug discovery. A few techniques are currently available to discover kinase substrate and map cell signaling. However, to augment kinase substrate discovery approaches, it is essential to develop alternative techniques. Pflum has recently discovered cosubstrate promiscuity of protein kinases with gamma-modified ATP analogs. Here, kinase-catalyzed biotinylation with ATP-biotin was used to develop novel tools to discover kinase substrates …