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Articles 1021 - 1050 of 2101
Full-Text Articles in Chemistry
Reactivity Of Ketyl And Acetyl Radicals From Direct Solar Actinic Photolysis Of Aqueous Pyruvic Acid, Alexis J. Eugene, Marcelo I. Guzman
Reactivity Of Ketyl And Acetyl Radicals From Direct Solar Actinic Photolysis Of Aqueous Pyruvic Acid, Alexis J. Eugene, Marcelo I. Guzman
Chemistry Faculty Publications
The variable composition of secondary organic aerosols (SOA) contributes to the large uncertainty for predicting radiative forcing. A better understanding of the reaction mechanisms leading to aerosol formation such as for the photochemical reaction of aqueous pyruvic acid (PA) at λ ≥ 305 nm can contribute to constrain these uncertainties. Herein, the photochemistry of aqueous PA (5-300 mM) continuously sparged with air is re-examined in the laboratory under comparable irradiance at 38° N at noon on a summer day. Several analytical methods are employed to monitor the time series of the reaction, including (1) the derivatization of carbonyl (C═O) functional …
Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu
Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu
Chemistry: Faculty Publications and Other Works
The Bacillus subtilis protein regulator of the gabTD operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5′-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the “active site” in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands. A reactive GABA analog, ( …
Hydrogen Peroxide Inhibition And Inactivation Of Bicupin Oxalate Oxidase, John M. Goodwin Vii
Hydrogen Peroxide Inhibition And Inactivation Of Bicupin Oxalate Oxidase, John M. Goodwin Vii
Master of Science in Chemical Sciences Theses
Oxalate oxidase is a manganese containing enzyme that catalyzes the oxygen dependent oxidation of oxalate to carbon dioxide and hydrogen peroxide. Oxalate oxidase from Ceriporiopsis subvermispora (CsOxOx) is the first characterized bicupin oxalate oxidase. Potential applications of oxalate oxidase in cancer treatment, paper pulping, and biofuel cells highlight the need to study the effects of hydrogen peroxide on the CsOxOx catalyzed oxidation of oxalate. Membrane inlet mass spectrometry (MIMS) was used to directly measure initial rates of carbon dioxide formation and oxygen consumption in varying initial concentrations of hydrogen peroxide. This work demonstrates that hydrogen peroxide is both a reversible …
Hierarchical Corannulene-Based Materials: Energy Transfer And Solid-State Photophysics, Allison M. Rice, W. Brett Fellows, Ekaterina A. Dolgopolova, Andrew B. Greytak, Aaron K. Vannucci, Mark D. Smith, Stavros G. Karakalos, Jeanette A. Krause, Stanislav M. Avdoshenko, Alexey A. Popov, Natalia B. Shustova Prof. Dr.
Hierarchical Corannulene-Based Materials: Energy Transfer And Solid-State Photophysics, Allison M. Rice, W. Brett Fellows, Ekaterina A. Dolgopolova, Andrew B. Greytak, Aaron K. Vannucci, Mark D. Smith, Stavros G. Karakalos, Jeanette A. Krause, Stanislav M. Avdoshenko, Alexey A. Popov, Natalia B. Shustova Prof. Dr.
Faculty Publications
We report the first example of a donor–acceptor corannulene-containing hybrid material with rapid ligand-to-ligand energy transfer (ET). Additionally, we provide the first time-resolved photoluminescence (PL) data for any corannulene-based compounds in the solid state. Comprehensive analysis of PL data in combination with theoretical calculations of donor–acceptor exciton coupling was employed to estimate ET rate and efficiency in the prepared material. The ligand-to-ligand ET rate calculated using two models is comparable with that observed in fullerene-containing materials, which are generally considered for molecular electronics development. Thus, the presented studies not only demonstrate the possibility of merging the intrinsic properties of π-bowls, …
Cytotoxic And Antimicrobial Effects Of Silver-Containing Surfaces, Sarah Goderecci
Cytotoxic And Antimicrobial Effects Of Silver-Containing Surfaces, Sarah Goderecci
Theses and Dissertations
This study examines applications of sputtered silver coatings as alternatives to traditional antibiotic treatments. Given the increase in reports of antibiotic-resistant bacteria, new treatments and coatings for in-dwelling medical devices such as catheters and orthopedic implants are necessary. Silver oxide films were deposited onto Ti surfaces to examine the efficacy of such coatings against a variety of bacterial species both in vitro and in vivo. Bacterial growth studies showed that coatings exhibited antimicrobial activity against a range of bacterial species acting either in a bacteriostatic or bactericidal mechanism, depending on the target. Limited toxicity to in vitro mammalian cells was …
Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch
Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch
UNO Student Research and Creative Activity Fair
Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …
Session C-1: Modeling Stem Activities Into Classroom Practice, Sowmya Anjur
Session C-1: Modeling Stem Activities Into Classroom Practice, Sowmya Anjur
Professional Learning Day
Students understand concepts better when they have had a chance to work hands on with relevant material. Examples will be presented from my classroom where difficult concepts have been modeled into simple experiments with considerable success in enhancing student understanding. Special focus will be given to selected topics that students seem to have the most difficulty grasping. The objective is to enable students to transfer their understanding to solve complex problems with considerable ease and apply their understanding to real world scenarios on assessments. Suggestions will also be provided for implementation of various concepts into the high school classroom.
Dual-Functional-Tag-Facilitated Protein Labeling And Immobilization, Xinyi Zhang, Wei Lu, Kevin Kwan, Dibakar Bhattacharyya, Yinan Wei
Dual-Functional-Tag-Facilitated Protein Labeling And Immobilization, Xinyi Zhang, Wei Lu, Kevin Kwan, Dibakar Bhattacharyya, Yinan Wei
Chemistry Faculty Publications
An important strategy in the construction of biomimetic membranes and devices is to use natural proteins as the functional components for incorporation in a polymeric or nanocomposite matrix. Toward this goal, an important step is to immobilize proteins with high efficiency and precision without disrupting the protein function. Here, we developed a dual-functional tag containing histidine and the non-natural amino acid azidohomoalanine (AHA). AHA is metabolically incorporated into the protein, taking advantage of the Met-tRNA and Met-tRNA synthetase. Histidine in the tag can facilitate metal-affinity purification, whereas AHA can react with an alkyne-functionalized probe or surface via well-established click chemistry. …
Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows
Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows
Biomedical Engineering Western Regional Conference
No abstract provided.
Hmba Is A Putative Hsp70 Activator Stimulating Hexim1 Expression That Is Down-Regulated By Estrogen, Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su Ph.D.
Hmba Is A Putative Hsp70 Activator Stimulating Hexim1 Expression That Is Down-Regulated By Estrogen, Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su Ph.D.
Chemistry Faculty Publications
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-a transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bisacetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation. However, the direct molecular targets of HMBA that modulate the induction of HEXIM1 expression in mammalian cells have not been identified. Based …
Multi-Instrument Comparison And Compilation Of Non-Methane Organic Gas Emissions From Biomass Burning And Implications For Smoke-Derived Secondary Organic Aerosol Precursors, Lindsay E. Hatch, Robert J. Yokelson, Chelsea E. Stockwell, Patrick R. Veres, Isobel J. Simpson, Donald R. Blake, John J. Orlando, Kelley C. Barsanti
Multi-Instrument Comparison And Compilation Of Non-Methane Organic Gas Emissions From Biomass Burning And Implications For Smoke-Derived Secondary Organic Aerosol Precursors, Lindsay E. Hatch, Robert J. Yokelson, Chelsea E. Stockwell, Patrick R. Veres, Isobel J. Simpson, Donald R. Blake, John J. Orlando, Kelley C. Barsanti
Chemistry and Biochemistry Faculty Publications
Multiple trace-gas instruments were deployed during the fourth Fire Lab at Missoula Experiment (FLAME- 4), including the first application of proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) and comprehensive two-dimensional gas chromatography-time-offlight mass spectrometry (GC×GC-TOFMS) for laboratory biomass burning (BB) measurements. Open-path Fourier transform infrared spectroscopy (OP-FTIR) was also deployed, as well as whole-air sampling (WAS) with onedimensional gas chromatography-mass spectrometry (GCMS) analysis. This combination of instruments provided an unprecedented level of detection and chemical speciation. The chemical composition and emission factors (EFs) determined by these four analytical techniques were compared for four representative fuels. The results demonstrate that the instruments are …
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Publications and Research
The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This …
Cyclipostins And Cyclophostin Analogs As Promising Compounds In The Fight Against Tuberculosis, Phuong Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin Martin, Rishi Paudel, Giri Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher Spilling, Jean-François Cavalier, Stéphane Canaan
Cyclipostins And Cyclophostin Analogs As Promising Compounds In The Fight Against Tuberculosis, Phuong Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin Martin, Rishi Paudel, Giri Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher Spilling, Jean-François Cavalier, Stéphane Canaan
Chemistry & Biochemistry Faculty Works
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM). This compound was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order …
Mechanistic Insights Into The Radical S-Adenosyl L-Methionine Enzyme Mftc, Bulat Khaliullin
Mechanistic Insights Into The Radical S-Adenosyl L-Methionine Enzyme Mftc, Bulat Khaliullin
Electronic Theses and Dissertations
Mycofactocin is a putative peptide-derived redox cofactor in Mycobacterium family. Its putative biosynthetic pathway is encoded by the operon mftABCDEF. The initial step of this pathway is a posttranslational modification of a peptide precursor MftA, which is catalyzed by MftC enzyme. This modification only occurs in the presence of chaperone MftB. Here, we demonstrate that MftC is a radical S-adenosyl L-methionine (SAM) enzyme and we examine its catalytic mechanism. We show that the modification of MftA requires two equivalents of SAM and is implemented in two steps: (i) the decarboxylation of a C-terminal tyrosine, resulting in formation of an …
Paper-Based Diagnostic Devices, Spencer A. Schultz, Isabelle C. Noxon, Tyler A. Sisley, Andres W. Martinez
Paper-Based Diagnostic Devices, Spencer A. Schultz, Isabelle C. Noxon, Tyler A. Sisley, Andres W. Martinez
Chemistry and Biochemistry
This chapter will provide an overview of existing diagnostic devices made primarily out of paper and then focus on paper-based microfluidic devices, the next generation of paper-based diagnostic devices that promises to extend the use of paper as a material for fabricating diagnostic devices well into the future.
Chapter Contents:
- 2.1 Introduction
- 2.2 Current paper-based diagnostic devices
- 2.2.1 Dipstick devices
- 2.2.2 Lateral-flow devices
- 2.2.2.1 Vertical-flow devices
- 2.2.3 Paper-based arrays
- 2.3 Paper-based microfluidic devices
- 2.3.1 Fabrication of paper-based microfluidic devices
- 2.3.2 Applications of paper-based microfluidic devices
- 2.4 Conclusions
- References
Airborne Measurements Of Western U.S. Wildfire Emissions: Comparison With Prescribed Burning And Air Quality Implications, Xiaoxi Liu, L. Gregory Huey, Robert J. Yokelson, Vanessa Selimovic, Isobel J. Simpson, Markus Müller, Jose L. Jimenez, Pedro Campuzano-Jost, Andreas J. Beyersdorf, Donald R. Blake, Zachary Butterfield, Yonghoon Choi, John D. Crounse, Douglas A. Day, Glenn S. Diskin, Manvendra K. Dubey, Edward Fortner, Thomas F. Hanisco, Weiwei Hu, Laura E. King, Lawrence Kleinman, Simone Meinardi, Tomas Mikoviny, Timothy B. Onasch, Brett B. Palm, Jeff Peischl, Ilana B. Pollack, Thomas B. Ryerson, Glen W. Sachse, Arthur J. Sedlacek, John E. Shilling, Stephen Springston, Jason M. St. Clair
Airborne Measurements Of Western U.S. Wildfire Emissions: Comparison With Prescribed Burning And Air Quality Implications, Xiaoxi Liu, L. Gregory Huey, Robert J. Yokelson, Vanessa Selimovic, Isobel J. Simpson, Markus Müller, Jose L. Jimenez, Pedro Campuzano-Jost, Andreas J. Beyersdorf, Donald R. Blake, Zachary Butterfield, Yonghoon Choi, John D. Crounse, Douglas A. Day, Glenn S. Diskin, Manvendra K. Dubey, Edward Fortner, Thomas F. Hanisco, Weiwei Hu, Laura E. King, Lawrence Kleinman, Simone Meinardi, Tomas Mikoviny, Timothy B. Onasch, Brett B. Palm, Jeff Peischl, Ilana B. Pollack, Thomas B. Ryerson, Glen W. Sachse, Arthur J. Sedlacek, John E. Shilling, Stephen Springston, Jason M. St. Clair
Chemistry and Biochemistry Faculty Publications
Wildfires emit significant amounts of pollutants that degrade air quality. Plumes from three wildfires in the western U.S. were measured from aircraft during the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) and the Biomass Burning Observation Project (BBOP), both in summer 2013. This study reports an extensive set of emission factors (EFs) for over 80 gases and 5 components of submicron particulate matter (PM1) from these temperate wildfires. These include rarely, or never before, measured oxygenated volatile organic compounds and multifunctional organic nitrates. The observed EFs are compared with previous measurements of temperate …
A Dual-Chamber Method For Quantifying The Effects Of Atmospheric Perturbations On Secondary Organic Aerosol Formation From Biomass Burning Emissions, Daniel S. Tkacik, Ellis S. Robinson, Adam Ahern, Rawad Saleh, Chelsea Stockwell, Patrick Veres, Isobel J. Simpson, Simone Meinardi, Donald R. Blake, Robert J. Yokelson, Albert A. Presto, Ryan C. Sullivan, Neil M. Donahue, Allen L. Robinson
A Dual-Chamber Method For Quantifying The Effects Of Atmospheric Perturbations On Secondary Organic Aerosol Formation From Biomass Burning Emissions, Daniel S. Tkacik, Ellis S. Robinson, Adam Ahern, Rawad Saleh, Chelsea Stockwell, Patrick Veres, Isobel J. Simpson, Simone Meinardi, Donald R. Blake, Robert J. Yokelson, Albert A. Presto, Ryan C. Sullivan, Neil M. Donahue, Allen L. Robinson
Chemistry and Biochemistry Faculty Publications
Biomass burning (BB) is a major source of atmospheric pollutants. Field and laboratory studies indicate that secondary organic aerosol (SOA) formation from BB emissions is highly variable. We investigated sources of this variability using a novel dual-smog-chamber method that directly compares the SOA formation from the same BB emissions under two different atmospheric conditions. During each experiment, we filled two identical Teflon smog chambers simultaneously with BB emissions from the same fire. We then perturbed the smoke with UV lights, UV lights plus nitrous acid (HONO), or dark ozone in one or both chambers. These perturbations caused SOA formation in …
In Situ Measurements Of Water Uptake By Black Carbon-Containing Aerosol In Wildfire Plumes, Anne E. Perring, Joshua P. Schwarz, Milos Z. Markovic, David W. Fahey, Jose L. Jimenez, Pedro Campuzano-Jost, Brett D. Palm, Armin Wisthaler, Tomas Mikoviny, Glenn Diskin, Glen Sachse, Luke Ziemba, Bruce Anderson, Taylor Shingler, Ewan Crosbie, Armin Sorooshian, Robert Yokelson, Ru Shan Gao
In Situ Measurements Of Water Uptake By Black Carbon-Containing Aerosol In Wildfire Plumes, Anne E. Perring, Joshua P. Schwarz, Milos Z. Markovic, David W. Fahey, Jose L. Jimenez, Pedro Campuzano-Jost, Brett D. Palm, Armin Wisthaler, Tomas Mikoviny, Glenn Diskin, Glen Sachse, Luke Ziemba, Bruce Anderson, Taylor Shingler, Ewan Crosbie, Armin Sorooshian, Robert Yokelson, Ru Shan Gao
Chemistry and Biochemistry Faculty Publications
Water uptake by black carbon (BC)-containing aerosol was quantified in North American wildfire plumes of varying age (1 to ~40 h old) sampled during the SEAC4RS mission (2013). A Humidified Dual SP2 (HD-SP2) is used to optically size BC-containing particles under dry and humid conditions from which we extract the hygroscopicity parameter, κ, of materials internally mixed with BC. Instrumental variability and the uncertainty of the technique are briefly discussed. An ensemble average κ of 0.04 is found for the set of plumes sampled, consistent with previous estimates of bulk aerosol hygroscopicity from biomass burning sources. The temporal evolution of …
Design, Synthesis And Biological Evaluation Of Histone Deacetylase (Hdac) Inhibitors: Saha (Vorinostat) Analogs And Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity, Ahmed Negmeldin
Wayne State University Dissertations
HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools …
Development Of Chemical Tools To Investigate Protein S-Glutathionylation In Response To Metabolic Alteration, Kusal Theekshana Gayan Samarasinghe
Development Of Chemical Tools To Investigate Protein S-Glutathionylation In Response To Metabolic Alteration, Kusal Theekshana Gayan Samarasinghe
Wayne State University Dissertations
Oxidative stress is a common characteristic of age-related diseases such as vascular diseases, diabetes and cancer. Many diseases are known to be regulated by glutathionylation. Glutathionylation is referred to as the formation of disulfide bond between a protein cysteine and a glutathione. To understand the molecular mechanisms behind the disease initiation and progression, identification of such glutathionylated proteins is important. Even though existing methods have been widely used, several limitations of these methods hinder the identification of such proteins in disease conditions. Therefore, we developed a versatile chemical method that generates clickable glutathione inside the cells. In this method, we …
Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo
Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo
Wayne State University Dissertations
In the development of finding a peptide targeting H69 of 23S rRNA in bacterial ribosomes, phage display was employed at pH 5.5, a buffer condition previously reported of H69 preferring a closed conformation. After sequencing, several peptides were chosen through sequence alignment, followed by preparation using solid-phase peptide synthesis. The peptides were characterized using MALDI-TOF and purified with HPLC. A truncated peptide TARHIY was selected from FID assay. Through binding studies using ESI-MS, SPR, BLItz, and NMR, the binding properties of the peptide to H69 were determined, such as binding affinity, stoichiometry, and interaction site. The peptide exhibited moderate binding …
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 …
Investigating Medicinally Important Portein-Protein And Protein-Ligand Interactions : A Computational Approach, Cooper Ashley Taylor
Investigating Medicinally Important Portein-Protein And Protein-Ligand Interactions : A Computational Approach, Cooper Ashley Taylor
Honors Theses
Molecular dynamics (MD) simulations and computational chemistry allow for an atomistic understanding of protein-protein and protein-ligand binding motifs. Through the use of MD, medicinally relevant complexes can be examined in detail unattainable by experimental methods. Within this work, systems pertinent to both Alzheimer’s Disease and HIV-1 are probed and thoroughly sampled to help elucidate potential therapeutic pathways. We used molecular dynamics and free energy estimations to gauge the affinity for the binary and ternary complexes of KLC1, APP and JIP1, three proteins all believed to be involved in the propagation of Alzheimer’s Disease. Two areas of thought exist suggesting that …
Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen
Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen
Chemistry Faculty Publications
Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …
Real-Time Investigation Of Bulky Lesion Bypass By Y-Family Dna Polymerase, Dpo4, Using Single Molecule Fret, Pramodha Liyanage
Real-Time Investigation Of Bulky Lesion Bypass By Y-Family Dna Polymerase, Dpo4, Using Single Molecule Fret, Pramodha Liyanage
Wayne State University Dissertations
DNA is constantly exposed to various DNA damaging agents that are generated by various internal and external sources. Some of this damage may not be able to be repaired by cellular machineries causing DNA replication to be blocked. Once the replication fork is blocked by a DNA adduct, damage tolerance DNA polymerases, mainly Y-family, are able to restore the DNA replication by synthesizing past the DNA adduct. Benzo[a]pyrene (B[a]P) is one of the most studied environmental carcinogens. It is known to make covalent DNA adducts after metabolic activation and the bulkiness of the B[a]P adducts impose a strong barrier to …
Isolation And Spectroscopic Characterization Of Zn(Ii), Cu(Ii), And Pd(Ii) Complexes Of 1,3,4-Thiadiazole-Derived Ligand, Dariusz Karcz, Arkadiusz Matwijczuk, Bozena Boron, Bernadette Creaven, Leszek Fiedor, Andrzej Niewiadomy, Mariusz Gagos
Isolation And Spectroscopic Characterization Of Zn(Ii), Cu(Ii), And Pd(Ii) Complexes Of 1,3,4-Thiadiazole-Derived Ligand, Dariusz Karcz, Arkadiusz Matwijczuk, Bozena Boron, Bernadette Creaven, Leszek Fiedor, Andrzej Niewiadomy, Mariusz Gagos
Articles
A series of complexes incorporating Zn(II), Cu(II), and Pd(II) ions, and 4-(5-heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (L1) as model ligand, was synthesized in order to examine the nature of potential interactions between biologically active ligands, 1,3,4-thiadiazoles and metal ions with proven biological relevance. The structures of the compounds isolated were characterized using a number of spectroscopic methods including IR, Uv–vis, AAS, steady state and time-resolved fluorescence (TRF). The results obtained suggest that the L1-Zn(II) and L1-Pd(II) complexes consist of one molecule of L1 and one acetate ion acting as ligands, while the L1-Cu(II) complex adapts a 2:1 (L1: metal) stoichiometry. The coordination of L1 …
Design, Synthesis And Biological Screening Of Novel Cucsinspired Estrone Analogues Towards Treatment Of Hepatocellular Carcinoma, Mater Hussen Mahnashi
Design, Synthesis And Biological Screening Of Novel Cucsinspired Estrone Analogues Towards Treatment Of Hepatocellular Carcinoma, Mater Hussen Mahnashi
Electronic Theses and Dissertations
Cucurbitacins (CUCS) are natural products with highly oxygenated tetracyclic triterpenes produced mostly by Cucurbitaceae family plant. They are known for their therapeutic efficiency with different biological activities, such as anti-inflammatory, hepatoprotective and anti-cancer. Hepatocellular carcinoma (HCC) is the third leading cause of death worldwide. Previous reports have shown the ability of CUCS to inhibit the growth of hepatocellular carcinoma cell lines (HepG-2) significantly. Structural activity relationship studies suggested the potential of the 23, 24 enone side chain of CUCS to bind to the Epidermal Growth Factor Receptor (EGFR). Due to the limited quantities of CUCS upon isolation and the challenges …
Enhancement Of The Physicochemical Properties Of Pt(Dien)(Nucleobase) (2+) For Hivncp7 Targeting, S. D. Tsotsoros, P. B. Lutz, A. G. Daniel, E. J. Peterson, R. E. F. De Paiva, E. Rivera, Y. Qu, C. A. Bayse, N. P. Farrell
Enhancement Of The Physicochemical Properties Of Pt(Dien)(Nucleobase) (2+) For Hivncp7 Targeting, S. D. Tsotsoros, P. B. Lutz, A. G. Daniel, E. J. Peterson, R. E. F. De Paiva, E. Rivera, Y. Qu, C. A. Bayse, N. P. Farrell
Chemistry & Biochemistry Faculty Publications
Physicochemical properties of coordination compounds can be exploited for molecular recognition of biomolecules. The inherent π-π stacking properties of [Pt(chelate)(N-donor)]2+([PtN4]) complexes were modulated by systematic variation of the chelate (diethylenetriamine and substituted derivatives) and N-donor (nucleobase or nucleoside) in the formally substitution-inert PtN4 coordination sphere. Approaches to target the HIV nucleocapsid protein HIVNCp7 are summarized building on (i) assessment of stacking interactions with simple tryptophan or tryptophan derivatives to (ii) the tryptophan-containing C-terminal zinc finger and (iii) to the full two-zinc finger peptide and its interactions with RNA and DNA. The xanthosine nucleoside was identified …
Cbl And Cbl-B Dictate Csf-1r Endocytic Traffic And Signaling In Macrophages, Lu Huang
Cbl And Cbl-B Dictate Csf-1r Endocytic Traffic And Signaling In Macrophages, Lu Huang
Electronic Theses and Dissertations
Macrophage colony stimulating factor receptor (CSF-1R or MCSFR) is a receptor tyrosine kinase essential for the growth and function of macrophages. Understanding the mechanisms that regulate CSF-1R activation and deactivation will provide insights to clinical treatment of macrophage related diseases including chronic inflammation and cancer. Previously, our laboratory showed that CSF-1R undergoes a novel membrane trafficking route that involves macropinocytosis to deactivate CSF-1R signaling. This thesis makes the discovery that the ubiquitin ligases Cbl and Cbl-b cooperate to regulate CSF-1R endocytosis and traffic to macropinosome in macrophages. Macrophages were derived from mice knocked out for Cbl, Cbl-b or the double …
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 …