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Articles 1 - 30 of 177
Full-Text Articles in Biochemistry
Recent Advances In Phosphatidylinositol Phosphate Kinases (Pipks) And Their Inhibitors, Mengxia Sun, Jian Hu, Xuefei Huang
Recent Advances In Phosphatidylinositol Phosphate Kinases (Pipks) And Their Inhibitors, Mengxia Sun, Jian Hu, Xuefei Huang
BAU Journal - Science and Technology
Phosphatidylinositol phosphate kinases (PIPKs) are an important class of enzymes in humans, which produce lipid signaling molecules playing central roles in pathogenesis of diseases such as cancer, neurodegenerative diseases, and viral infection. Consequently, they are attracting increasing attention as drug targets for disease treatment. This review summarizes the functions of the PIPK family enzymes and highlights recent efforts on designing novel inhibitors against PIPKs. These advances are extensively discussed to stimulate interest in this field and promote further development of highly potent and selective inhibitors for innovative therapeutic applications.
Isolation, Purification, And Characterization Of Α-Galactosidase From Watermelon (Citrullus Lanatus), Christopher Henley Jr.
Isolation, Purification, And Characterization Of Α-Galactosidase From Watermelon (Citrullus Lanatus), Christopher Henley Jr.
Chemistry & Biochemistry Undergraduate Honors Theses
The enzyme α-galactosidase is a type of glycosidase that removes galactose sugar units from larger molecules in cells. Compounds that inhibit glycosidases have been useful for understanding the structure and function of the enzymes they inhibit, and some have been used to treat certain diseases. Using inhibitors of α-galactosidase to study its characteristics and mechanisms may provide insights into its role in disease and its general utility. Advances in fields such as agriculture, sustainable fuels, and biomedicine may be facilitated by inhibition studies of α-galactosidase, but the current library of known inhibitors is relatively lacking. Obtaining α-galactosidase enzymes from chemical …
Increased Backbone Rigidity Of Artificial Transcription Factors, Jasmine Glover, Emma Otey, Joanna K. Kwao, Nicholas Truex
Increased Backbone Rigidity Of Artificial Transcription Factors, Jasmine Glover, Emma Otey, Joanna K. Kwao, Nicholas Truex
Senior Theses
Programming DNA-binding proteins is an effective strategy for developing therapeutics that regulate gene expression. These proteins can directly bind to DNA to activate or repress transcription of specific genes. Zinc finger proteins are a class of DNA-binding proteins commonly found in eukaryotic organisms. Their DNA-binding function is derived from unique amino acid sequences within each domain that recognizes specific nucleotides, allowing each finger to selectively recognize three DNA base pairs. Adjoining of multiple domains in tandem allows recognition of a specific DNA sequence. Artificial transcription factors can be made of multiple zinc finger domains arranged in tandem and engineered to …
Design And In Silico Modeling Of Heterocyclic-Based Xanthone Derivatives As Potential Anticancer Agents Through Tyrosine Kinase Inhibition, Yehezkiel Steven Kurniawan, Ervan Yudha, Nela Fatmasari, Radite Yogaswara, Harno Dwi Pranowo, Eti Nurwening Sholikhah, Jumina Jumina
Design And In Silico Modeling Of Heterocyclic-Based Xanthone Derivatives As Potential Anticancer Agents Through Tyrosine Kinase Inhibition, Yehezkiel Steven Kurniawan, Ervan Yudha, Nela Fatmasari, Radite Yogaswara, Harno Dwi Pranowo, Eti Nurwening Sholikhah, Jumina Jumina
Makara Journal of Science
Cancer is one of the deadliest diseases nowadays, and tyrosine kinase receptors play crucial roles in cancer cell survival, differentiation, proliferation, and migration. This study designed and developed a new inhibitor from heterocyclic-based xanthone derivatives to target two tyrosine kinase receptors, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), through in silico screening. Eighteen heterocyclic-based xanthones were evaluated through molecular docking for both receptors. All heterocyclic-based xanthones gave the root mean square deviation (RMSD) value lower than 2.00 Å. Xanthone with isobenzothiazole substituent (iBzThio) was found as the most potent inhibitor with binding energies of -10.60 and …
Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain
Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain
Dissertations, Theses, and Capstone Projects
Chapter 1: A glycan detection platform comprised of synthetic carbohydrate receptors (SCRs) immobilized onto polymer brushes was prepared. SCR043, an alkene-containing SCR, was incorporated into grafted-from polymer brushes using hypersurface photolithography, resulting in microarrays of SCR043-functionalized polymer brushes, where brush height (h) and SCR grafting density (Γ) is controlled precisely at each feature in the array. The influence of h and Γ on the binding to five fluorescently labelled monosaccharides – α-glucose (α-Gluc-FL), α-galactose (α-Gal-FL), α-mannose (α-Man-FL), β-glucose (β-Gluc-FL), and β-galactose (β-Gal-FL) – in aqueous buffer …
The Chemistry Of Red Lipstick: The Impact Red Lipstick Has On Society, Lilliana Weldeslassie
The Chemistry Of Red Lipstick: The Impact Red Lipstick Has On Society, Lilliana Weldeslassie
Electronic Theses & Dissertations (2024 - present)
Cosmetic chemistry is deeply embedded in everyday life, shaping the products people use from morning to night. Among these, red lipstick stands out as a formulation that blends complex chemistry with a cultural meaning. This thesis examines the scientific foundations of red lipstick through its chemical composition, pigment structure, toxicological history, analytical methods, and evolving sustainability practices. Historically, red lipsticks relied on high-risk ingredients such as lead, mercury, and other toxic metals, reflecting an era before chemical safety and regulatory oversight were incorporated.21 Modern formulations have established safer synthetic dyes, natural waxes, plant-based oils, and stabilizers created to optimize …
Bio-Orthogonal Chemistry-Based Strategy To Turn-On And Turn-Off Crispr-Cas9 Gene Editing In Solution And In Live Cells, Bhoomika Pandit
Bio-Orthogonal Chemistry-Based Strategy To Turn-On And Turn-Off Crispr-Cas9 Gene Editing In Solution And In Live Cells, Bhoomika Pandit
Electronic Theses & Dissertations (2024 - present)
The CRISPR–Cas9 system is a widely popular tool for genome engineering. There is a strong interest in developing tools for temporal control of CRISPR-Cas9 activity to address some of the challenges and to broaden the scope of potential applications. In this thesis I describe two biorthogonal based approaches to either Turn-ON and Turn-OFF CRISPR-Cas9 gene editing.
In first project work I describe a bio-orthogonal chemistry-based approach to Turn-ON Cas9 nuclease activity with temporal precision. We report a TCO-acylimidazole reagent that acylates 2′-OH groups of RNA. Poly-acylation (“cloaking”) of RNA was optimized in vitro using a model 18-nt oligonucleotide, as well …
Photo And Spatial Control Of Rna Structures And Functions: Exploring Positional Effects And Photo-Responsiveness Of Azobenzene Modified Nucleotides, Jinxi Du
Electronic Theses & Dissertations (2024 - present)
RNA molecules perform many important biological functions by forming complex three-dimensional structures stabilized by base pairing, tertiary interactions, and metal ion coordination. Because RNA function depends strongly on its structure, methods that allow reversible control of RNA conformation and activity are important for understanding RNA behavior and for potential therapeutic applications. However, achieving reversible and site-specific control of RNA structure, especially at the single-nucleotide level, remains challenging. In this dissertation, I developed and applied azobenzene-modified nucleotides as a chemical tool to enable optical and spatial control of RNA structure and function.
The first part of this dissertation focuses on establishing …
Exploring The Limitations Of Substrate Scope In Dimethylallyltryptophan Synthases, Evan T. Miller
Exploring The Limitations Of Substrate Scope In Dimethylallyltryptophan Synthases, Evan T. Miller
Theses and Dissertations--Pharmacy
Natural products (NPs), are the largest source of bioactive compounds in Nature, and are essential to the treatment of human disease. Nearly 50% of drugs approved for use from 1981 to 2019 owe some aspect of their development to NPs, either in terms of their structure, pharmacophore, or mechanism of action. However, NPs are difficult to structurally optimize. Chemoenzymatic methods for NP derivatization have been increasingly seen as practical alternatives to traditional synthetic methods. Prenyltransferases (PTs) are involved in the primary and secondary metabolism of plants, bacteria, and fungi, and they are key enzymes in the biosynthesis of many clinically …
An Investigation Into The Potential Role Of Thioester Bonds In Prebiotic Atp Synthesis, Adam J. Ruf
An Investigation Into The Potential Role Of Thioester Bonds In Prebiotic Atp Synthesis, Adam J. Ruf
Williams Honors College, Honors Research Projects
In this project I will attempt to show a potential prebiotic pathway for the synthesis of ATP. This pathway involves the use of thioester bond containing molecules, as derivatives of these bonds have been shown to exhibit enzyme-like catalytic properties. Nuclear magnetic resonance spectroscopy will be utilized to characterize each step of the pathway to ensure it is successful.
Aptamer Selection And Development Of Electrochemical Aptamer-Based Sensors For Neuropeptide Y, Evelyn Adela Carreto Guevara
Aptamer Selection And Development Of Electrochemical Aptamer-Based Sensors For Neuropeptide Y, Evelyn Adela Carreto Guevara
Department of Chemistry: Dissertations, Theses, and Student Research
In this thesis, we report the results of four aptamers obtained from an aptamer selection process called the systematic evolution of ligands by exponential enrichment (SELEX) with affinity to Neuropeptide Y (NPY). NPY is a highly abundant peptide transmitter with widespread distribution throughout the body which affects various physiological functions. These functions include energy homeostasis, appetite regulation, stress response, and anxiety regulation. Dynamic monitoring of NPY levels is crucial for better understanding behaviors in individuals with neurological disorders associated with NPY. Aptamers are synthetic oligonucleotides obtained through SELEX which have a binding affinity to a target of interest when in …
Du Undergraduate Showcase Abstracts: Research, Scholarship, And Creative Works, Kabe Aberle, Nadia Kako, Kateri Mcrae, Brooke Agulnek, Sky Palmon, Yasmine Ramirez, Francisca Aguirre Beltran, Ashley Juarez, Bridget Kim, Tessa Appel, Sterling Kerr, Spencer Ingley, Gabe Meyer, Robin Tinghitella, Dale Broder, Lily Baeza, Chloe Beers, Julia Coakley, Whitney Kelsey, Sydney Gainforth, Gabi Wing, Audrey Martin, Aaliyah Amore Berry, Brooke Watley, Kiruthika Venkatesan, Rachel Bienstock, Annabella Brotherston, Madison Bryant, Mia Burgener, Emma P. Lieb, Rachel A. Johnson, Jennifer L. Hoffman, Kania Campbell, Kiena Campbell, Courtney Cassidy, Sage Krzyzkowski, Maddox Jones, Skylar Abookire, Luke Hawkins, Sunnah Yoon, Andrea Chu, Yan Qin, Nyah Cubbison, Brian Gearity, Daniel Mcintosh, Mariely Cruz, Edward Garrido, Grady Dionne, Nicole Doris, Lyndsie Salvagio, Ann-Charlotte Granholm-Bentley, Anna Dymov, Hannah Eckert, Gabrielle Welsh, Erica Larson, Charlie Ernst, Anna Zhou, Sarah Watamura, Larissa Fedorovich-Klein, Georgie Fields, Kimberly A. Guevara, Aven Mccall, Ben Peltier, Feruz Yahia, Patrick Flores, Jadyn Floyd, Sophia Forcier, J. Von R. Monteza, Peter Sokol-Hessner, Gwendolyn Geiger, Scott Nichols, Camryn Gunter, Kendal Hengst, Charlie Bednarz, Issy Garside, Addison Baker, Rachel Mina, Brooke Hermanson, Amanda Klingler, William Highfill, Sydney Jaques, Kerstin Lewey, Allison Grossery, Daniel Linseman, Ethan Lim, Jagger Livengood, Owen Mantelli, Gabby Pappas, Abby Mcdonald, Madeleine Dierking, Eve Miller, Emma Loeber, Anna Marlow, Michael Kerwin, Ella Mathews, Hillary Hamann, Khadija Mohamed, Vivian Nguyen, Gabri Notov, Ifunayachi Ogbonna-Ukuku, Sunil Kumar, Charles Baysah, Sarah Olson, Don Sullivan, Anna Paradiso, Jay Parrish, Mira Pronobis, Alisha Pravasi, Kerstin Haring, Diego Ramirez, Christopher Reardon, Juliana Ramirez, Casey Doherty, Ella Kestner, Teagan Weindel, Cate Billings, Pablo Torre-Walter, Lucy Rand, Samantha Reynolds, Mark Siemens, Khadeeja Rashid, Laine Satterlee, Piper Heilbronner, Lily Pound, Ben Whitehurst, Anna Respet, Lizzie Lesoing, Sydney Hertel, Aya Saad-Masri, Brooke Ballenger, Max Proske, Hannah Rosenberg, Ellia Nakahara, Sophia Espinoza, Ivan Woolhouse, Simon Ruland, Gorkem Er, Timothy Sweeny, Melaku Saketa, Michela Schenk, Maren Lynch, Madi Hamm, Grace Schroeder, Michelle Rozenman, Rana Seif, Jackson Hall, Marisela Simental, Daniel Paredes, Aaron Mena, Preston Spaan, Evelyn Stovin, David Andrew Swartz, Anh Tran, Daniel Pittman, Luke Farchione, Emily Boyer, Ukari Verner, Lacey Conrad, Jonathan Velotta, James Weiner, Jagger Gossett, Noah Sherry, Sam Proud, Ben Block, Avi Narayana, Zoey Weiss, Alyssa Wilson, Gabrielle Walsh, David Zonana, Keely Wright, Kena Riveria, Lillybelle Deer, Jena Doom, Elysia Davis, Isabelle Yaremenko, Caitlyn Young
Du Undergraduate Showcase Abstracts: Research, Scholarship, And Creative Works, Kabe Aberle, Nadia Kako, Kateri Mcrae, Brooke Agulnek, Sky Palmon, Yasmine Ramirez, Francisca Aguirre Beltran, Ashley Juarez, Bridget Kim, Tessa Appel, Sterling Kerr, Spencer Ingley, Gabe Meyer, Robin Tinghitella, Dale Broder, Lily Baeza, Chloe Beers, Julia Coakley, Whitney Kelsey, Sydney Gainforth, Gabi Wing, Audrey Martin, Aaliyah Amore Berry, Brooke Watley, Kiruthika Venkatesan, Rachel Bienstock, Annabella Brotherston, Madison Bryant, Mia Burgener, Emma P. Lieb, Rachel A. Johnson, Jennifer L. Hoffman, Kania Campbell, Kiena Campbell, Courtney Cassidy, Sage Krzyzkowski, Maddox Jones, Skylar Abookire, Luke Hawkins, Sunnah Yoon, Andrea Chu, Yan Qin, Nyah Cubbison, Brian Gearity, Daniel Mcintosh, Mariely Cruz, Edward Garrido, Grady Dionne, Nicole Doris, Lyndsie Salvagio, Ann-Charlotte Granholm-Bentley, Anna Dymov, Hannah Eckert, Gabrielle Welsh, Erica Larson, Charlie Ernst, Anna Zhou, Sarah Watamura, Larissa Fedorovich-Klein, Georgie Fields, Kimberly A. Guevara, Aven Mccall, Ben Peltier, Feruz Yahia, Patrick Flores, Jadyn Floyd, Sophia Forcier, J. Von R. Monteza, Peter Sokol-Hessner, Gwendolyn Geiger, Scott Nichols, Camryn Gunter, Kendal Hengst, Charlie Bednarz, Issy Garside, Addison Baker, Rachel Mina, Brooke Hermanson, Amanda Klingler, William Highfill, Sydney Jaques, Kerstin Lewey, Allison Grossery, Daniel Linseman, Ethan Lim, Jagger Livengood, Owen Mantelli, Gabby Pappas, Abby Mcdonald, Madeleine Dierking, Eve Miller, Emma Loeber, Anna Marlow, Michael Kerwin, Ella Mathews, Hillary Hamann, Khadija Mohamed, Vivian Nguyen, Gabri Notov, Ifunayachi Ogbonna-Ukuku, Sunil Kumar, Charles Baysah, Sarah Olson, Don Sullivan, Anna Paradiso, Jay Parrish, Mira Pronobis, Alisha Pravasi, Kerstin Haring, Diego Ramirez, Christopher Reardon, Juliana Ramirez, Casey Doherty, Ella Kestner, Teagan Weindel, Cate Billings, Pablo Torre-Walter, Lucy Rand, Samantha Reynolds, Mark Siemens, Khadeeja Rashid, Laine Satterlee, Piper Heilbronner, Lily Pound, Ben Whitehurst, Anna Respet, Lizzie Lesoing, Sydney Hertel, Aya Saad-Masri, Brooke Ballenger, Max Proske, Hannah Rosenberg, Ellia Nakahara, Sophia Espinoza, Ivan Woolhouse, Simon Ruland, Gorkem Er, Timothy Sweeny, Melaku Saketa, Michela Schenk, Maren Lynch, Madi Hamm, Grace Schroeder, Michelle Rozenman, Rana Seif, Jackson Hall, Marisela Simental, Daniel Paredes, Aaron Mena, Preston Spaan, Evelyn Stovin, David Andrew Swartz, Anh Tran, Daniel Pittman, Luke Farchione, Emily Boyer, Ukari Verner, Lacey Conrad, Jonathan Velotta, James Weiner, Jagger Gossett, Noah Sherry, Sam Proud, Ben Block, Avi Narayana, Zoey Weiss, Alyssa Wilson, Gabrielle Walsh, David Zonana, Keely Wright, Kena Riveria, Lillybelle Deer, Jena Doom, Elysia Davis, Isabelle Yaremenko, Caitlyn Young
DU Undergraduate Research Journal Archive
Abstracts from the DU Undergraduate Research Showcase.
Lighting Up The Cell: Developing A Luminescent Lanthanide Probe For Detecting Rnas, Jonathan Savell
Lighting Up The Cell: Developing A Luminescent Lanthanide Probe For Detecting Rnas, Jonathan Savell
Honors Projects
An anion detecting luminescent probe, Tb:DO2A-Cs124, was repurposed for use in RNA imaging. Potential RNA aptamers were identified for the molecule using Capture-SELEX and MinION sequencing. Fluorimetry data revealed these aptamers did not allow for the probe to luminesce in the presence of target RNAs due to adenosine monophosphate’s ability to quench the emission signal.
Trenching And Compost Sustain Grain Yield Increases Over Nine Years On Deep Sands But At A Cost, David J.M. Hall, Tom J. Edwards
Trenching And Compost Sustain Grain Yield Increases Over Nine Years On Deep Sands But At A Cost, David J.M. Hall, Tom J. Edwards
Grain and Other Field Crops Research Articles
Context. Crops grown on deep sands on the south coast of WA are limited by soil physical and chemical properties including compaction and poor nutrition. Aims. Crops grown on deep sands on the south coast of Western Australia are limited by soil physical and chemical properties including compaction and poor nutrition. Our aim was to determine what effects deep-placed organic amendments have on soil properties and crop production in a deep sand and whether such amendments are profitable. Methods. A long-term field trial was conducted over nine years (2015–2023) to investigate soil amendments including lime (0 and …
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Electronic Theses and Dissertations
Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.
A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …
Transient Transmembrane-Electrostatically Localized Protons And Transmembrane Potential In A Laser Flashed Bacteriorhodopsin Purple Membrane Open Flat Sheet - Summary, James Weifu Lee
Chemistry & Biochemistry Faculty Publications
The transmembrane-electrostatically localized protons/cations charges (TELCs, also known as TELPs) model may serve as a unified framework to explain a wide range of bioenergetic phenomena. Transient transmembrane-electrostatically localized protons (TELPs) and transmembrane potential in a laser flash-energized bacteriorhodopsin (bR) purple membrane (PM) open flat sheet are now better analyzed. Under the Heberle et al. (1994) experimental conditions, the number of bR molecules is now calculated to be 8200 per PM open flat sheet with a diameter of 600 nm. With a single-turnover laser flash intensity of 3 mJ/cm² to photoexcite 10% of the bR molecules, the laser flash-induced peak TELCs …
Experimental Demonstration And Study Of Transmembrane-Electrostatically Localized Protons Prevail, James Weifu Lee
Experimental Demonstration And Study Of Transmembrane-Electrostatically Localized Protons Prevail, James Weifu Lee
Chemistry & Biochemistry Faculty Publications
In this review in relation to some interesting arguments from Silverstein, it is now reaffirmed that the experimental demonstration of transmembrane-electrostatically localized protons (TELPs) was successfully accomplished through 1) using an aluminum film as a TELPs sensor in a biomimetic anode water-membrane-water cathode system, 2) analyzing the water-electrolysis current curve, and 3) measuring bulk liquid phase pH. Formation of induced TELPs was subsequently discovered in an anode water-membrane-water-membrane-water cathode system. The discovery of induced TELPs enabled clean experimental tests on the cation-TELPs exchange process by using sodium bicarbonate or potassium bicarbonate solution in the central liquid chamber. The sodium/TELPs exchange …
Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore
Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore
Master's Theses
Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …
Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani
Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani
Al-Bahir
This study seeks to provide a comprehensive overview of the latest progress in the antioxidant properties of nanoparticles. Nanoparticles (NPs) have emerged as a promising tool in several domains of science and industry, including their application as antioxidant agents. The main knowledge gaps seem to be in correctly identifying the make-up of the naturally occurring phytochemicals that give these nano-antioxidants their extraordinary pharmacology and drug-like properties. In many instances, that characterization is done using spectroscopy instrumentation such as fourier-transform Infrared (FT-IR), scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). From literature appraisals, it was discovered that a lot of …
Development Of Platinum(Iv)-Gold(I)-Based Anticancer Agents, Javier E. Lopez-Hernandez
Development Of Platinum(Iv)-Gold(I)-Based Anticancer Agents, Javier E. Lopez-Hernandez
Dissertations, Theses, and Capstone Projects
Heterometallic compounds have emerged as prospective multitarget anticancer drugs. These species may display improved efficacy and physicochemical properties compared to the individual metallic fragments, while helping combat drug resistance by exerting effects on multiple pathways. In this thesis we describe the synthesis of new bi- and tri-metallic compounds based on platinum(IV) compounds containing FDA-approved platinum agents, and gold(I) derivatives with known anticancer properties. We demonstrate their toxicity and selectivity against a small panel of renal, bladder, ovarian, and breast cancer cell lines, as well as their synergistic effects. We have selected a trinuclear PtAu2compound containing the Pt(IV) core …
Design, Synthesis, And Optimization Of Allosteric Inhibitors Of Hiv-1 Integrase, Krunal H. Patel
Design, Synthesis, And Optimization Of Allosteric Inhibitors Of Hiv-1 Integrase, Krunal H. Patel
Dissertations
The human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with …
Chm116 Principles Of Chemistry Ii Lecture Slides, Leah S. Cohen, Probal Banerjee
Chm116 Principles Of Chemistry Ii Lecture Slides, Leah S. Cohen, Probal Banerjee
Open Educational Resources
This file contains the lecture slides that are used in CHM116, Principles of Chemistry II.
Design, Synthesis, And Evaluation Of Class Iia Histone Deacetylase (Hdac) Inhibitors, Lauren Nicole Kotsull
Design, Synthesis, And Evaluation Of Class Iia Histone Deacetylase (Hdac) Inhibitors, Lauren Nicole Kotsull
Wayne State University Dissertations
Histone deacetylase (HDAC) proteins are linked to disease states, including cancer, and have become important targets for therapeutic development. Many inhibitors have been developed to target HDAC proteins, including FDA-approved inhibitors Vorinostat (SAHA), Belinostat, Romidepsin, and Panobinostat. These inhibitors non-specifically influence most of the 11 metal-dependent HDAC isoforms, which might contribute to the side effects that patients experience during treatment. The lack of selectivity also diminishes the use of HDAC inhibitors as biomedical research tools. To address these drawbacks, the development of selective inhibitors has been heavily studied. Yet, reported inhibitors are predominantly selective for class I HDAC isoforms (HDACs …
Illuminating Function And Enabling Inhibition At The Protein-Membrane Interface Of Glutathione Peroxidase 4., Courtney L. Labrecque
Illuminating Function And Enabling Inhibition At The Protein-Membrane Interface Of Glutathione Peroxidase 4., Courtney L. Labrecque
Theses and Dissertations
Membrane proteins act as gateways to cells and are responsible not only for signaling, lipid transport, and cellular homeostasis, but they are also integral in disease pathologies. One class of membrane proteins, peripheral membrane proteins (PMPs), reside in aqueous compartments of the cell until they are recruited to the membrane to perform their function. Glutathione peroxidase 4 (GPx4) is a PMP enzyme responsible for engaging the membrane and reducing lipid hydroperoxides, thereby preventing cellular death via ferroptosis. Due to its central function surrounding ferroptosis, GPx4 is an interesting drug target that has recently gained interest for inflammatory diseases as well …
The Role Of Sugars In Aggregation Of The Protein Kassinin, Lillie G. Waldron
The Role Of Sugars In Aggregation Of The Protein Kassinin, Lillie G. Waldron
Student Summer Scholars Manuscripts
The aggregation of proteins to form amyloids is implicated in several diseases such as Alzheimer’s Disease, Parkinson’s Disease, and many others. This aggregation has several stages, progressing from isolated protein molecules (monomers) to small aggregates (oligomers), which are toxic to cells, and finally to large, string-like mature aggregates. Despite this association with disease, functional amyloids, which have normal biological functions, also result from protein aggregation. Kassinin, an amphibian peptide involved in nerve signal transmission, is a model system for functional amyloid study. To compare the aggregation of functional and disease-causing amyloids, we previously synthesized a fluorine-labeled kassinin through solid-phase peptide …
Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte
Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte
Markey Cancer Center Faculty Publications
Brain insulin resistance links the failure of energy metabolism with cognitive decline in both type 2 Diabetes Mellitus (T2D) and Alzheimer’s disease (AD), although the molecular changes preceding overt brain insulin resistance remain unexplored. Abnormal biliverdin reductase-A (BVR-A) levels were observed in both T2D and AD and were associated with insulin resistance. Here, we demonstrate that reduced BVR-A levels alter insulin signaling and mitochondrial bioenergetics in the brain. Loss of BVR-A leads to IRS1 hyper-activation but dys- regulates Akt-GSK3β complex in response to insulin, hindering the accumulation of pGSK3βS9 into the mito- chondria. This event impairs oxidative phosphorylation and fosters …
Chemical Synthesis Of Sensitive Dna, Komal Chillar
Chemical Synthesis Of Sensitive Dna, Komal Chillar
Dissertations, Master's Theses and Master's Reports
Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …
Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye
Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye
Theses and Dissertations--Chemistry
Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs, cancer continues to be a leading cause of death in the United States. Metallodrugs, especially Au complexes, have played a prominent role in the search for the next generation of chemotherapeutic agents. Herein, I report on the synthetic strategies towards the rational design of stable Au (Au)-based agents, study their reactivity in biological environment, and offer insights into the cytotoxic mechanism of action in cancer. Chemotherapeutic Au compounds exist mainly in +I or +III oxidation states. Repurposing of the Au(I) FDA approved auranofin for the treatment of diseases …
Hybridization And Duplex Stability Of Peptide Nucleic Acid Containing An Azobenzene Switch, Carmen J. Velasquez
Hybridization And Duplex Stability Of Peptide Nucleic Acid Containing An Azobenzene Switch, Carmen J. Velasquez
College of Graduate Studies: Theses & Dissertations
Light-driven molecular switches that can be turned on and off on demand have found many biological applications. For DNA, RNA, and synthetic derivatives, the switch can be used to interfere with a hybridization event with a complementary strand. To explore this potential, we have synthesized three light-sensitive PNA which have an azobenzene group (PNA-5azo5 and PNA-4azo4), and two azobenzene groups (PNA-2azo5azo2) as part of the PNA backbone. UV experiments were used to verify the conversion to the cis-isomer from the initial trans state for all of the single-stranded Azo-PNA ( PNA-5azo5, PNA-4azo4, and PNA-2azo5azo2) by irradiating at 365 nm …
Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin
Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin
Dissertations, Master's Theses and Master's Reports
Synthetic long oligodeoxynucleotides (ODNs) have found wide applications in diverse fields such as chemical biology, synthetic biology, and genes and genomes synthesis. Those applications leading to a significant demand for their production. However, traditional methods for purifying synthetic ODNs present notable drawbacks, particularly their inability to purify long ODNs, rendering long ODN synthesis challenging. To address these issues, chemical synthesis techniques for long ODNs coupled with non-chromatographic purification methods have been developed. This technology makes the purification of long synthetic ODNs feasible and offers a viable pathway for producing genes and genomes with extensive repeats or stable secondary structures, which …