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Articles 31 - 60 of 112

Full-Text Articles in Biochemistry

Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama May 2019

Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama

Biological Sciences

Hypoglycemia is a state of abnormally low blood glucose. Many patients who use insulin, primarily for the treatment of diabetes, experience multiple bouts of hypoglycemia, termed recurrent hypoglycemia (RH). Because RH impairs cognitive function and ability to appropriately respond to a subsequent episode of hypoglycemia, it is critical to develop treatments. One approach, which we have taken here, is to attempt to preserve neuronal fuel supply during a hypoglycemic episode. Medium-chain triglycerides are medium-chain fatty acid (MCT) esters of glycerol that can provide an alternative fuel source to the brain via ketones; the hippocampus is known to express transporters for …


Significance Of Rna 2'-5' Linkage And Metal-Ion Mediated Base Pairs, Fusheng Shen Jan 2019

Significance Of Rna 2'-5' Linkage And Metal-Ion Mediated Base Pairs, Fusheng Shen

Legacy Theses & Dissertations (2009 - 2024)

It has been known that the template-directed RNA chemical replication reaction produces mixture of backbones containing both 3’-5’ and 2’-5’ linkages. This backbone heterogeneity has been a significant problem in studying the emergence of RNA World from the prebiotic chemistry. However, very recently, it is reported that FMN binding aptamer and a hammerhead ribozyme are still able to retain considerable functions in the presence of certain 2’-5’ linkages, indicating that RNA backbones may be quite flexible and this backbone heterogeneity problem may not be as severe as originally thought. This finding also brings two related important questions: First, how does …


Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy Jan 2019

Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy

Legacy Theses & Dissertations (2009 - 2024)

DksA is a bacterial gene regulator that functions synergistically with the stress alarmone ppGpp to mediate the stringent response. DksA also functions independently of ppGpp to regulate transcription of a number of genes. DksA function is dependent on its binding affinity to RNA polymerase and requires specific interactions between RNAP and catalytic amino acids located on the coiled coil tip, D74 and A76. While much of the previous work on DksA has focused on understanding the mechanisms of action and the numerous gene targets for transcriptional regulation, little is known about the mechanisms by which DksA expression and function may …


Inteins From Pathogenic Microbes As Regulatory Elements And Potential Drug Targets, Cathleen Maria Schiraldi Jan 2019

Inteins From Pathogenic Microbes As Regulatory Elements And Potential Drug Targets, Cathleen Maria Schiraldi

Legacy Theses & Dissertations (2009 - 2024)

Inteins are self-splicing elements that orchestrate the autocatalytic process of protein splicing, during which the intein excises itself from a host polypeptide. This multistep reaction involves a series of coordinated nucleophilic attacks and peptide bond rearrangements that remove the intein and reassemble the flanking halves, called exteins, to form the mature host protein. Some inteins are also mobile elements, and can spread to the same or ectopic sites using an internal homing endonuclease domain.


Evaluation Of Fingerprint Content For Forensic Crime Scene Analysis And Drug Metabolite Detection, Erica Kathryn Brunelle Jan 2019

Evaluation Of Fingerprint Content For Forensic Crime Scene Analysis And Drug Metabolite Detection, Erica Kathryn Brunelle

Legacy Theses & Dissertations (2009 - 2024)

With respect to criminal investigations, one key piece of evidence that often gets overlooked are fingerprints. For years, fingerprint samples have been believed to be useful only for matching purposes using their unique ridges, shapes, and sizes. With the rapid growth of forensic science, it has become evident that the development of fingerprint analysis has been stagnant. The traditional approach has been advantageous for the identification of many individuals; however, many fingerprint samples have been labeled “unusable” due to smudging, smearing, or any one of a myriad of reasons that could cause inconclusive matches. These samples can, however, still be …


Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods Jan 2019

Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods

Legacy Theses & Dissertations (2009 - 2024)

DksA is a global transcription factor that binds RNAP directly to regulate the expression of many genes and operons, including ribosomal RNA, in a ppGpp-dependent or ppGpp–independent manner. It is also involved in facilitating the process of DNA replication by removing stalled transcription elongation complexes that could block the progress of the replication fork. In addition, DksA is important for colonization, establishment of biofilms, and pathogenesis. In order to sustain these various functions, an adequate level of cellular DksA is required. This work tested the hypothesis that the E. coli dksA is substantially regulated at the level of transcription. Using …


Sers For Protein Detection At A Single Molecule Level For Developing A New Medical Diagnostics Platform, Lamyaa Almehmadi Jan 2019

Sers For Protein Detection At A Single Molecule Level For Developing A New Medical Diagnostics Platform, Lamyaa Almehmadi

Legacy Theses & Dissertations (2009 - 2024)

A two-step process of protein detection at a single molecule level using Surface Enhanced Raman Spectroscopy (SERS) was developed as a new platform for medical diagnostics in this proof-of-concept study. First, a protein molecule was bound to a linker in the bulk solution and then this adduct was chemically reacted with the SERS substrate. Traut’s Reagent (TR) was used to thiolate Bovine serum albumin (BSA) in solution followed by chemical cross linking to a gold surface through a sulfhydryl group. A Glycine-TR adduct was used as a control sample to identify the protein contribution to the SER spectra. Gold SERS …


Defining And Harnessing Nature's Selection Of Geranylation In Rna Modification, Phensinee Haruehanroengra Jan 2019

Defining And Harnessing Nature's Selection Of Geranylation In Rna Modification, Phensinee Haruehanroengra

Legacy Theses & Dissertations (2009 - 2024)

Natural RNAs utilize extensive chemical modifications to diversify their structures and functions. Geranylated-2-thiouridine is a special hydrophobic tRNA modification that has been discovered very recently in several bacteria, namely E. coli, E. aerogenes, P. aeruginosa and S. typhimurium by Liu group. It has been found as a post-transcription modification on the wobble position of anticodon of tRNAs specific for glutamic acid, glutamine and lysine. Geranylated-tRNA was shown to correct the frameshifting during the translation of E. coli. However, the reason of the existing of the modification is still largely unclear. To understand why nature incorporates such a hydrophobic group in …


Saliva As A Diagnostic Biological Fluid And The Human Salivary Proteome, Jessica Ghassan Emsies Jan 2019

Saliva As A Diagnostic Biological Fluid And The Human Salivary Proteome, Jessica Ghassan Emsies

Legacy Theses & Dissertations (2009 - 2024)

Saliva is a unique biologic fluid that contains a varying spectrum of proteins, nucleic acids, electrolytes, and hormones.31 It is an exocrine secretion of the salivary glands which is hypotonic in nature with a pH of 7.2-7.4.31 Saliva plays an important role in the oral cavity.33 It lubricates, hydrates, and bathes the oral cavity, therefore, aiding speech and mastication.33 Saliva forms a barrier on the teeth, protects against demineralization, and aids in remineralization.33 Saliva is required for chewing and food bolus preparation, it contains enzymes necessary for digestion, and mediates the sense of taste.33 It also helps wound healing and …


Rack1 Is A Critical Component In Ires-Mediated Translation, Ethan Asher Lafontaine Jan 2018

Rack1 Is A Critical Component In Ires-Mediated Translation, Ethan Asher Lafontaine

Legacy Theses & Dissertations (2009 - 2024)

Due to its sheer number of interacting partners, core ribosomal protein RACK1 is a key player in many cellular processes and has been shown to play a vital role of translation initiation of the Hepatitis C virus RNA. The HCV 5′ untranslated region contains an internal ribosome entry site. IRES-mediated translation is a process employed in eukaryotes by select viruses and some cellular mRNAs by which translation initiation bypasses the canonical mRNA cap-dependent pathway by means of an RNA secondary structure (the IRES). While cap-dependent translation requires the recruitment of a suite of initiation factors, IRES-mediated translation requires few to …


Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu Jan 2018

Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu

Legacy Theses & Dissertations (2009 - 2024)

Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient’s life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is …


Dna Functionalized Nanoparticles In Nanobiosensor And Sensor Array Development For Molecular Diagnostics And In Vitro Identification Of Biomolecules, Mustafa Salih Hizir Jan 2018

Dna Functionalized Nanoparticles In Nanobiosensor And Sensor Array Development For Molecular Diagnostics And In Vitro Identification Of Biomolecules, Mustafa Salih Hizir

Legacy Theses & Dissertations (2009 - 2024)

Nucleic acid technology along with vast variety of nanomaterials has demonstrated a great potential in many applications from biosensing studies to molecular diagnostics, from biomedical and bioanalytical research to environmental analysis. Especially short single stranded (ss) DNA molecules, called oligonucleotides, are extraordinary biopolymers featuring diverse functionality on the nanoparticles thanks to their high degree of programmability, target-specific binding or cleavage, molecular recognition ability, structure-switching capability, and unique interactions at the bio-nano interfaces. Among those, there have been many biosensing applications utilizing ss DNAs and numerous nanomaterials through various detection techniques such as fluorometric, colorimetric or electrochemical methods. Although many groundbreaking …


The Dissemination, Regulatory Role, And Evolution Of Mycobacterial Inteins, Danielle Skye Kelley Jan 2018

The Dissemination, Regulatory Role, And Evolution Of Mycobacterial Inteins, Danielle Skye Kelley

Legacy Theses & Dissertations (2009 - 2024)

Inteins are intervening protein elements, capable of coordinating escape from a host protein through a self-catalyzed mechanism, called protein splicing. This results in free intein and a mature host protein product. Inteins are also mobile elements and many contain homing endonucleases that enable the targeting to ectopic sites and invasion of novel niches. Inteins have been found across all three domains of life and are often present in replication, recombination, and repair proteins. However, it is unclear if the observed distribution is simply a factor of endonuclease preference or if inteins have been selectively maintained due to an adaptation that …


Circular Rna : A Review Of History, Diseases, And Diagnostic Potential, Daniel Conley Jan 2018

Circular Rna : A Review Of History, Diseases, And Diagnostic Potential, Daniel Conley

Legacy Theses & Dissertations (2009 - 2024)

Abstract


Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl Jan 2018

Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl

Legacy Theses & Dissertations (2009 - 2024)

Prior studies of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, including that of GluA3 AMPA receptor subunit, have shown that alternative mRNA splicing, which generates flip and flop variants with different amino acid sequences, gives rise to functional differences between the two variants. The goal of this MS thesis is to investigate the basic gating properties of the heteromeric complex channels formed from GluA2R/GluA3 AMPA receptor subunits and the different variants between the two subunits. The hypothesis to be tested is whether different GluA3 variants affect the channel gating properties when each of the variants is in a complex with the Q/R-site edited …


Functional Modulation Of Ampa Receptors By R/G Editing And Auxiliary Subunits, Wei Wen Jan 2018

Functional Modulation Of Ampa Receptors By R/G Editing And Auxiliary Subunits, Wei Wen

Legacy Theses & Dissertations (2009 - 2024)

The propagation of information in the central nervous system is, in essence, the flow of ions. Neurons connect with each other to form neural circuits that perform distinct functions, and these connections are formed through synapses. Excitatory and inhibitory synapses determine the excitability of a neuron, which further dictates the firing of action potentials. The major ion channels that mediate the transmission at the excitatory synapses are ionotropic glutamate receptors, among which AMPA receptors are responsible for the fast excitatory transmission. Therefore, the functionalities of AMPA receptors substantially affect the information flow, and dysfunction of them could potentially cause many …


The Development Of Bioaffinity-Based Concepts For On-Site Forensic Analyses : Blood, Sweat, And ... Fingerprints?, Crystal Huynh Jan 2018

The Development Of Bioaffinity-Based Concepts For On-Site Forensic Analyses : Blood, Sweat, And ... Fingerprints?, Crystal Huynh

Legacy Theses & Dissertations (2009 - 2024)

There have been many advances in forensic science over the recent years, but a majority of the tests currently preformed are still heavily reliant upon laboratory-based processes. This means that valuable pieces of information are left unexamined until a crime scene has been completely processed and evidence is moved to a crime lab. In some cases, the evidence may even be left in a queue due to backlogs from previous cases. The delay resulting from the time necessary for crime scene processing and transportation, as well as additional time spent waiting on lab equipment availability, hinders an investigator’s ability to …


Genetically Engineered Polypeptides As Biomimetic Light Harvesting Optical Antenna, Jason P. Seeley Jan 2018

Genetically Engineered Polypeptides As Biomimetic Light Harvesting Optical Antenna, Jason P. Seeley

Legacy Theses & Dissertations (2009 - 2024)

Natural resources useful for the generation of energy are limited. The development of efficient materials capable of utilizing the abundant free solar radiation is of considerable interest. Utilization of otherwise wasted energy sources, including solar radiation, is a progressive step in the quest for sustainable energy. Solar radiation incident upon the earth’s surface exceeds current energy requirements and motivates scientists to investigate and develop functional devices and nanomaterials including light harvesting complexes (LHC) capable of capturing solar radiation for energy conversion and storage.


Raman Spectroscopy And Chemometrics For Forensic Bloodstain Analysis : Species Differentiation, Donor Age Estimation, And Dating Of Bloodstains, Kyle C. Doty Jan 2017

Raman Spectroscopy And Chemometrics For Forensic Bloodstain Analysis : Species Differentiation, Donor Age Estimation, And Dating Of Bloodstains, Kyle C. Doty

Legacy Theses & Dissertations (2009 - 2024)

The field of forensic science is constantly growing, so the advancement of old and unreliable techniques is at the forefront of what will lead to future progress and improvement. Current methods for identification and analysis of bloodstains are underwhelming due to the insignificant amount of information provided in a destructive, unreliable, and unsafe manner. As is the purpose of this research, creating new methodologies that are rapid, nondestructive, robust, statistically reliable, and safe would significantly advance the way bloodstains are currently analyzed, while providing more useful and relevant information for investigations and criminal proceedings. Raman spectroscopy, along with advanced statistical …


Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan Jan 2017

Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan

Legacy Theses & Dissertations (2009 - 2024)

The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of …


Novel Approaches To Mitigating Bacterial Biofilm Formation And Intercellular Communication, Stephen Kasper Jan 2017

Novel Approaches To Mitigating Bacterial Biofilm Formation And Intercellular Communication, Stephen Kasper

Legacy Theses & Dissertations (2009 - 2024)

Long thought of as solitary single-cell organisms, it is now widely accepted that bacteria can act and cooperate as social organisms. Phenomena such as biofilm formation and quorum sensing (QS) are two intimately intertwined cooperative behaviors that significantly contribute to the pathogenesis of many bacteria. Biofilms are surface associated communities of bacteria encased in a secreted extracellular matrix, which provides several advantages over an individualized lifestyle, such as increased protection from antimicrobial agents as well as enhanced opportunity for the exchange of genetic material. Bacterial QS is a system of population-based communication through the production, sensing, and response to chemical …


Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan Jan 2017

Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan

Legacy Theses & Dissertations (2009 - 2024)

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, is an intracellular pathogen that infects millions of people every year. Mtb can survive inside the host for extended periods of time by sensing and adapting to the host environmental stressors. Transcriptional gene regulation plays a critical role in this adaptation. This dissertation focuses on understanding the structural and functional aspects of one such transcriptional regulatory unit, Cmr (Rv1675c), in Mtb.


Study Of Biologically Important Macromolecules By Nuclear Magnetic Resonance, Christopher Michael Demott Jan 2017

Study Of Biologically Important Macromolecules By Nuclear Magnetic Resonance, Christopher Michael Demott

Legacy Theses & Dissertations (2009 - 2024)

Intrinsically disordered proteins or unstructured segments within proteins play an important role in cellular physiology and pathology. A combination of peptide aptamers selected by using the yeast-two-hybrid scheme, and in-cell NMR identified high affinity binders to a transiently structured intrinsically disordered proteins (IDP). This method was validated using the prokaryotic ubiquitin-like protein, Pup, of the Mycobacterium proteasome. We discover two peptide aptamers that bind to opposite sites of a transient helix in Pup, an intrinsically disordered protein, that have vastly different effects on the survival of Mycobacterium bovis BCG.


Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction For Molecular Diagnostics And Bioanalytical Applications, Md Muhit Rana Jan 2017

Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction For Molecular Diagnostics And Bioanalytical Applications, Md Muhit Rana

Legacy Theses & Dissertations (2009 - 2024)

DNA nanotechnology has shown great promise in molecular diagnostic, bioanalytical and biomedical applications. The great challenge of detecting target analytes, biomarkers and small molecules, in molecular diagnostics is low yield sensitivity. To address this challenge, different nanomaterials have been used for a long time and to date there is no such cost-effective bioanalytical technique which can detect these target biomarkers (DNA, RNA, circulating DNA/miRNA) or environmental heavy metal ions (Hg2+ and Ag+) in a cost-effective and efficient manner.


A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen Jan 2017

A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen

Legacy Theses & Dissertations (2009 - 2024)

Insufficient activity of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate ion channels is involved in neurological disorders and developmental problems, such as schizophrenia, one of the most serious psychiatric diseases. Use of regulatory agents to enhance AMPA receptor activity under the circumstance has been shown therapeutically beneficial. Specifically, small-molecule compounds generally termed as potentiators or positive modulators of AMPA receptors have long been pursued as drug candidates for a potential treatment of these neurological disorders and diseases. The goal of my MS thesis work is to investigate the mechanism of potentiation on AMPA receptor by a classic potentiator known as CX546. The …


The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky Jan 2017

The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky

Legacy Theses & Dissertations (2009 - 2024)

Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …


Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich Jan 2017

Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich

Legacy Theses & Dissertations (2009 - 2024)

RNA post-transcriptional modifications (PTMs) are dynamic features that can be up- or down-regulated by the health and metabolic state of a cell. These covalent modifications are installed and removed on RNA nucleosides by enzymes controlled by the activation and deactivation of specific genes. The goal of this research was to demonstrate that RNA PTMs can serve as a unique feature for the classification/identification of microorganisms. We utilized a scheme based on electrospray ionization mass spectrometry (ESI-MS) to obtain global PTM profiles from total RNA extracted from various microorganisms in optimal growth conditions as well as Salmonella typhimurium (S. typhimurium) spiked …


A Kinetic Study Of Regulation Of Glua1 Homomeric And Heteromeric Ampa Receptors By 2,3-Benzodiazepines, Yin-Shuo (Andrew) Wu Jan 2017

A Kinetic Study Of Regulation Of Glua1 Homomeric And Heteromeric Ampa Receptors By 2,3-Benzodiazepines, Yin-Shuo (Andrew) Wu

Legacy Theses & Dissertations (2009 - 2024)

AMPA receptors are a subtype of the ionotropic glutamate receptor family. They are ligand-gated or glutamate-activated, transmembrane ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. AMPA receptors are essential for neuronal development and brain functions, including learning and memory. Over-activation of calcium permeable AMPA receptors has been linked to some neurological diseases such as stroke, Alzheimer’s disease and amyotrophic lateral sclerosis. Inhibitors of glutamate receptors are therefore drug candidates for the potential treatment of these neurological diseases. One of the most promising classes of AMPA receptor antagonists is 2,3-benzodiazepine derivatives, thought to be …


Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro Jan 2017

Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro

Legacy Theses & Dissertations (2009 - 2024)

The challenges to forensic body fluid analysis have placed limitations on the type of information that investigators can acquire and how that information can be collected. In recent years, Raman spectroscopy has proven itself useful for characterizing body fluids. In 2008, a large-scale investigation was undertaken to explore the use of Raman spectroscopy as a means of identifying body fluids. This work resulted in multidimensional Raman spectroscopic signatures for the five main body fluids: semen, peripheral blood, saliva, vaginal fluid, and sweat. These studies were incredibly successful and created the foundation for years of continued research. Accordingly, the studies included …


Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega Jan 2017

Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega

Legacy Theses & Dissertations (2009 - 2024)

The allosteric regulation of SIRT6 by nicotinamide (NAM), along with the growing evidence of this enzyme's key role in the immune response, prompted the mechanistic study of SIRT6 inhibition by pyrazinamide (PZA) and analogs. In our current study, PZA, an analog of NAM, was revealed to have a modest modulatory effect on SIRT6, an enzyme that regulates the NF-κB signaling pathway at the transcriptional level (a relevant pathway to inflammation). Similarly, the analogs of PZA, 5-Cl PZA, 5-MeO PZA, and POA exhibited a modulatory effect against SIRT6 in our in vitro studies, enabling identification of a potential new target for …