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Folic Acid-Targeted Polymeric Complex Imprinted With Doxorubicin And Quercetin For Controlled Drug Delivery In Cancer Therapy, Ceren Türkcan, Emi̇rhan İşeri̇

Turkish Journal of Chemistry

​Cancer therapy is often limited by the systemic toxicity and dose-dependent adverse effects of conventional chemotherapeutic agents such as doxorubicin (DOX). In this study, a folic acid-functionalized molecularly imprinted polymeric complex based on poly(HEMA) crosslinked with ethylene glycol dimethacrylate was synthesized for the controlled release of DOX in combination with quercetin (QUE), a flavonoid known for its antioxidant and chemosensitizing properties. The aim of this work was to develop and physicochemically characterize a preliminary targeted drug delivery platform at a material-design level. The polymeric complex was synthesized via free-radical polymerization following a DOX–QUE precomplex formation step. Structural characterization was performed …

Synthesis, Structural Elucidation, In Vitro Antibacterial Activity Of Mononuclear Ag(I) Complex Derived From (E)-N-(4-Fluorophenyl)-1-(Pyridin-2-Yl) Methanimine And Triphenylphosphine Ancillary Ligand., Olufemi Stephen Odulaja, Saliu Alao Amolegbe, Muritala Adeniyi Olusola

Tanzania Journal of Science

Chemo-therapeutic application of metal complexes to remediation and subjugation of emerging infectious diseases with a view to improving potency and efficacy of a variety of drugs is gaining more momentum, especially in the 21st century. This research work designed a new biologically active complex [AgL(PPh3)2]NO3,C, obtained from the reaction of Ag(I) nitrate with bidentate pyridinyl Schiff base ligand (E)-N-(4-fluorophenyl)-1-(pyridin-2-yl) methanimine L, with triphenylphosphine (PPh3) as co-ligand. Characterisation was done by FT-IR, UV-Vis, NMR, (TGA/DTA), X-ray crystallography, and elemental analysis. The combined effects of pyridinyl Schiff base ligand and PPh3 on the antibacterial activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, …

Design, Synthesis, And Bioevaluation Of Moxifloxacin Hydrazide Metal Complexes: Integrated Spectroscopic, Computational, Antimicrobial, And Anticancer Investigations, Abbas Mamdoh Abbas, Sara Reda Fisal, Ibrahim A.I. Ali, W. Christropher Boyd, Haitham F. Kalil, Adel Sayed Orabi

Chemistry Faculty Publications

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H2O)Cl(MOX-H)2]Cl & centerdot;2.5H2O, [Ni(H2O)Cl(MOX-H)2]Cl.4.5H2O, [VO(MOX-H)2]SO4.3.5H2O, [Gd (H2O)(MOX-H)2(NO3)2]NO3.2H2O, and [Cu(MOX-H)2(H2O)Cl]Cl & centerdot;xH2O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, …

Investigating The Structure And Bioactivity Of Lanthanum Coordination Compounds, Shantanu Kadam, Bhushan Dhale, Bapu Yamgar, Swaminath Bhattar

Turkish Journal of Chemistry

Lanthanum metal complexes were synthesized using a classical condensation method by reacting lanthanum nitrate salts with a bidentate ligand in a 1:2:1 molar ratio (M:L:L). The formation and structure of the resulting complexes were confirmed through a combination of analytical techniques, including Fourier transformation infrared spectroscopy, thermal gravimetric analysis, X-ray diffraction, elemental microanalysis, and scanning electron microscopy. The lanthanum complexes synthesized exhibited strong in vitro antimicrobial activity. Antibacterial screening showed inhibition zones of 18–26 mm against Staphylococcus aureus and Escherichia coli, surpassing those of the reference drug ciprofloxacin (16–20 mm). Antifungal studies demonstrated inhibition zones of 15–23 mm against Candida …

Development And Validation Of An Analytical Method For Quantitative Determination Of Small Aldehydes In Plasma, Stephanie T. Clark

Chemistry & Biochemistry Theses - Archive

Small aldehydes such as formaldehyde and acetaldehyde are highly reactive metabolites that play important roles in biological processes related to oxidative stress, metabolism, and DNA damage. Because of their chemical reactivity, volatility, and low endogenous concentrations, accurate measurement of these compounds in biological samples remains analytically challenging. The goal was to develop and evaluate a practical analytical method for detecting small aldehydes in biologically relevant matrices using headspace gas chromatography mass spectrometry (HS-GC-MS). The method combined chemical derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and headspace sampling to stabilize aldehydes and enable selective detection by mass spectrometry. Method development focused on optimizing derivatization …

Application Of Paper Spray Mass Spectrometry For Screening Acetylcholinesterase Inhibitors, Diksha Gautam

Graduate Research Theses & Dissertations

Paper spray mass spectrometry (PS-MS) is a novel ambient ionization method that allows chemical and biological samples to be rapidly analyzed with little preparation being required. In this paper, PS-MS was set up and streamlined as an acetylcholinesterase (AChE)-monitoring platform in addition to screening an existing and newly produced AChE-inhibitors. The detection of the substrate, acetylcholine (m/z 146), and the AChE catalysis product, choline (m/z 104) was performed without applying chromatographic separation or derivatization to the dried paper substrates. Assay conditions were optimized in a systematic way, to develop a robust MS-compatible enzymatic workflow.

Calibration curves for both, acetylcholine and …

Electrochemical Characterization And Modulation Of Biological Processes, Yue-Qi Li, Wei-Hua Huang, De-Chen Jiang, Bao-Hong Liu, Bin Su, Yang Tian, Jing-Juan Xu, Ping Yu, Feng Zhao, Huang-Xian Ju, Jing-Hong Li

Journal of Electrochemistry

Electrochemical processes lie at the core of biological function, governing energy transduction, metabolic flux, and molecular signaling. Recent advances in electrochemical science now allow these processes to be probed and controlled with unprecedented spatial, temporal, and chemical resolution. In this review, we present an integrated framework that progresses from fundamental mechanisms to analytical technologies and functional modulation. We begin by outlining electron transfer pathways in mitochondrial respiration, microbial extracellular electron transfer, and DNA- and protein-based charge conduction, followed by the principles of photon-electron conversion in photosynthesis and the central role of redox equilibrium in coordinating cellular responses. We then highlight …

The Malonate Template: The Key To Unlocking Novel Amino Acids, Thomas Owens

Dissertations

The “Malonate Template” provides access to various amino acids, all from a common intermediate. Herein, demonstrates the use of the malonate template to establish a synthetic route to both 2-thiohistidine and 2-thio-3-N-methyl-histidine from a benzyl methyl malonate derived intermediate. Furthermore, efforts exploiting the applicability of the malonate template for the of both 2-thiohistidine and 2-thio-3-N-methyl-histidine as a suitable alternative to methods previously described by Erdelmeier are described.

The method presented incorporates modifications to the biomimetic pathway described by Erdelmeier for the synthesis of 2-thiohisidine. By exploiting the biomimetic formation of 2-thiohisitidne’s mechanism via mass spectrometry, we …

Synthesis And Evaluation Of Bodipy-, Azabodipy- And Chlorin-Based Conjugates For Imaging And Photodynamic Therapy Of Egfr-Overexpressing Cancers, Simran Dhingra

LSU Doctoral Dissertations

This dissertation discusses the design of EGFR-targeted small-molecule agents that unite molecular imaging with photodynamic therapy. Chapter 1 frames the clinical need for early detection and selective treatment and surveys BODIPY, aza-BODIPY, and chlorin scaffolds as tunable chromophores for near-infrared imaging and photosensitization. It also outlines EGFR as a validated target and compares two ligand classes used throughout this work: the tyrosine kinase inhibitor erlotinib and the cyclic peptide KLARLLT.

Chapter 2 describes the synthesis of a near-IR BODIPY bearing either one or two erlotinib units. Docking and SPR show specific interactions with the EGFR kinase domain, and both conjugates …

Bodipy-Based Photocages For The Controlled Release Of Hydrogen Sulfide And Persulfides, Yanmei Li

Dissertations

Reactive sulfur species (RSS) such as hydrogen sulfide (H2S) and hydropersulfides (RSSH) are crucial mediators in a variety of physiological and pathological processes. Their regulatory roles span from maintaining cellular redox balance to influencing signaling pathways critical for homeostasis and stress responses. This dissertation investigates H2S and RSSH as biologically important molecules and explores the development of boron-dipyrromethene (BODIPY)-based photocages for its controlled, light-triggered release. Given H2S and RSSH's critical role in redox regulation and cellular protection, achieving spatiotemporal control over its delivery is essential for both therapeutic and research applications. BODIPY scaffolds offer favorable photophysical properties, including visible-light activation …

1,3,4-Thiadiazole Derivatives As Pi3ks Inhibitor: Design, In Silico Studies, Synthesis, Characterization, And Antimicrobial Evaluation, Dharmvir Singh, Pankaj Kumar, Anoop Kumar, Vivek V. Bhosale, Kalicharan Sharma, Deepak Kumar, Ramchander Khatri, Tanuj Hooda, Amit Lather

Turkish Journal of Chemistry

Since PI3Ks are targeted by a variety of bacterial pathogens, they represent a promising target for host-directed immune therapy and may be beneficial in managing persistent bacterial infections. In the present study, computational studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives for phosphoinositide-3-kinases (PI3Ks) inhibitors were carried out using dock scores, Glide scores, and the MMGBSA dG method, with comparison to standard drugs (ofloxacin and fluconazole). A series of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives (D1-D17) were synthesized and evaluated for their in vitro antimicrobial activity against both gram-positive and gram-negative bacterial strains, as well as fungal strains, using the tube dilution method. The synthesized compounds were characterized …

Synthesis Of Sensitive Oligodeoxynucleotides Containing Acylated Cytosine, Adenine, And Guanine Nucleobases, Komal Chillar, Rohith Awasthy, Marina Tanasova, Shiyue Fang

Michigan Tech Publications

Background/Objective: Oligodeoxynucleotides (ODNs) containing base-labile modifications such as N4-acetyldeoxycytidine (4acC), N6-acetyladenosine (6acA), N2- acetylguanosine (2acG), and N4-methyoxycarbonyldeoxycytidine (4mcC) are highly challenging to synthesize because standard ODN synthesis methods require deprotection and cleavage under strongly basic and nucleophilic conditions, and there is a lack of ideal alternative methods to solve the problem. The objective of this work is to explore the capability of the recently developed 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) method for the incorporation of multiple 4acC modifications into a single ODN molecule and the feasibility of using the method for the incorporation of the 6acA, 2acG and 4mcC modifications into ODNs. Methods: …

Infrared Laser Ablation Of Biomolecules From Formalin-Fixed Tissue, Blessing Chisom Egbejiogu

LSU Doctoral Dissertations

In the research described in this dissertation, a high-precision infrared laser ablation microsampling method was utilized for spatially resolved proteomic and lipidomic analyses of formalin fixed paraffin embedded (FFPE) tissue, a widely used archival sample in biomedical research. Despite its extensive use, FFPE tissue presents challenges for proteomic analysis due to protein cross-linking and modifications introduced during fixation, which can hinder extraction and identification. Developing a streamlined high-resolution method to recover biomolecules from FFPE samples is critical for advancing biomarker discovery, retrospective studies, and multi-omics research. To address these challenges, this study employs an infrared (IR) laser ablation microdissection system …

A New Water-Soluble Silicon Phthalocyanine That Catalyzes The Photodegradation Of Pollutant Dyes, Damla Nur Kaya, Behi̇ce Sebnem Sesalan

Turkish Journal of Chemistry

The removal of color arising from water-soluble dyes in wastewaters is necessary to counter the threat to health. Because of thedifficulty in elimination of these dyes by conventional methods, their photodegradation using photosensitizers such as phthalocyanines(Pcs) has been employed recently. When compared to peripherally substituted derivatives, silicon Pcs are reported to be morebiocompatible with low toxicity. Thus a new silicon Pc substituted with two quaternized dimethylamino phenoxy units (compound 1)and its quaternized derivative (compound 2) were synthesized to test its photocatalytic ability employing the dyes methylene blue (MB),eosin B (EB), erythrosine (ERB), sulforhodamine B (SRB), and brilliant blue FCF (BRB), …

Chemistry Of Metalloguanines: An Overview Of Their Synthesis Routes And Their Implementations For The Period 2000-2024, Farah Saadoon Jaafar, Mahasin F. Alias

Karbala International Journal of Modern Science

Guanine has a variety of roles in chemistry, from its basic function in the storing and transferring genetic information to its usages in synthetic chemistry and other fields. Because of its distinct structure and biological importance, it is a fundamental component of contemporary study in organic chemistry and molecular biology.

In this review, we focused on covering the synthetic pathways of various derivatives of guanine from the year 2000 until the present. As a result of the guanine molecule containing multiple functional groups, this gives us the ability to prepare several guanines such as O⁶-alkylating guanines, O^{6 …}

Development And Applications Of Capillary Vibrating Sharp-Edge Spray Ionization Coupled With Atmospheric Pressure Chemical Ionization (Cvssi-Apci), Madison Elizabeth Pursell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mass spectrometry (MS) is a technique that is used in fields in which both complex and non-complex mixtures are analyzed. The state-of-the-art ion sources that are utilized for MS are being demonstrated to be functional for direct infusion of samples as well as for use with online separations. However, ion sources, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) can encounter problems such as ion suppression and an inability to ionize based on size and/or polarity, respectively. Further these sources are bulky and require gas flow, heat sources, and additional high voltage power supplies for optimal performance. …

The Utilization Of Alcohol Dehydrogenase (Adh) Enzymes In Stereocontrolled Synthesis, Gaurav Pramod Kudalkar

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Clostridium acetobutylicum alcohol dehydrogenase (CaADH) has been shown to catalyze the stereoselective reduction of a broad array of carbonyl compounds. This study uses a Hammett linear free-energy relationship (LFER) analysis to gain insight into CaADH enzyme mechanism across three substrate classes: aryl aldehydes, aryl β-keto esters, and aryl trifluoromethyl ketones. Kinetic data were collected by monitoring NADPH fluorescence, and Michaelis-Menten kinetics were applied. Hammett plots reveal that hydride transfer is rate-limiting for aldehydes and β-keto esters (ρ > 0), while it is proposed that dehydration is rate-limiting for trifluoromethyl ketones (ρ < 0). ¹³C NMR confirmed significant hydration in trifluoromethyl ketones. The …

Increased Thermal Stability And Retained Antibacterial Properties In A Sulbactam And Amantadine Salt: Towards Effective Antibacterial-Antiviral Combination Therapies, Josephine Bicknell, Ivan Bondarenko, Alice Colatrella, Elani J. Cabrera-Vega, Jesus Daniel Loya, Delbert S. Botes, Jay L. Mellies, Gonzalo Campillo-Alvarado

Chemistry Faculty Publications and Presentations

A clinically relevant multidrug solid comprising sulbactam (β-lactamase inhibitor) and amantadine (antiviral) displays enhanced thermal stability and sustained antibacterial activity compared to starting materials.

We describe the formation of a multidrug salt comprising sulbactam (SUL, β-lactamase inhibitor) and amantadine (AMNH, antiviral). Physicochemical investigation of the SUL·AMNH salt revealed enhanced thermal stability compared to pristine starting materials. In vitro studies found that salt formation in SUL·AMNH does not disrupt antibacterial activity against model organisms Escherichia coli and Staphylococcus epidermidis. To our knowledge, we show the first β-lactamase inhibitor-antiviral salt where both components have been approved by the U.S. Food and Drug …

The Application Of High-Resolution Mass Spectrometry For The Analysis Of Biopolymers, Metabolites, And Biologically Relevant Small Molecules, Christ Duc Tran

Graduate Doctoral Dissertations

High-resolution mass spectrometry (HRMS), as its name suggests, possesses high resolving power that enables the separation of ions with very close mass values. This is particularly beneficial for analyzing complex samples where numerous compounds may have similar masses, as it helps prevent signal overlaps and ensures an accurate spectral analysis. The current work explores the diverse applications of high-resolution mass spectrometry in oligonucleotide research, organic synthesis and medicinal chemistry. Oligonucleotide research: Chapters 2-5 present the research results from studies that employed ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) to understand the pharmacokinetics of RNA interference (RNAi) therapeutics. The …

New Imidazolidindionedioximes And Their Pt(Ii) Complexes: Synthesis And Investigation Of Their Antitumoral Activities On Breast Cancer Cells, Emrah Karahan, Tuğba Gençoğlu Katmerli̇kaya, Emel Önal, Aydan Dağ, Ayşe Gül Gürek, Vefa Ahsen

Turkish Journal of Chemistry

Breast cancer is one of the most common types of cancer worldwide and has the most lethality ratio for females among all cancers. Although current cancer therapeutics have made considerable advancements, there is still room for improvement in terms of efficacy. Many anticancer drugs have a risk of causing serious adverse effects due to their non-specific cytotoxic effects on both tumor and healthy cells. New therapeutics might have a greater ability to kill cancer cells, reduce the volume of tumors, and improve overall therapy response rates. Herein, we report the efficient synthesis and characterization of three amphi vic-dioximes and their …

Synthesis And Characterization Of New Hexahydroquinoline Derivatives, Evaluation Of Their Cytotoxicity, Intracellular Ros Production And Inhibitory Effects On Inflammatory Mediators, Ezgi̇ Pehli̇vanlar, Deni̇z Arca Çakir, Sonia Sanajou, Hülya Tezel Yalçin, Terken Baydar, Pinar Erkekoğlu, Hani̇fe Avci, Rahi̇me Şi̇mşek

Turkish Journal of Chemistry

Inflammation is a response to injury and infection in the organism. It can be categorized as acute and chronic inflammation. Chronic inflammation is the underlying cause of many diseases such as Alzheimer's, diabetes, rheumatoid arthritis, atherosclerosis and cardiovascular diseases. Recent studies have proven the anti-inflammatory properties of 1,4-dihydropyridines (1,4-DHPs) and its derivatives, which have many biological properties including calcium channel blockers. The structures of the synthesized compounds were elucidated by IR, 1H-NMR, 13C-NMR and HRMS methods. The cytotoxic properties of the compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in 3T3 cell line. Among the 15 compounds, the three compounds …

Synthesis Of Addressable Libraries: New Lessons And The Need For Proper Characterization For Microelectrode Array-Based Reactions, Albert Huang

Arts & Sciences Graduate Student Theses and Dissertations

The Moeller group has been developing synthetic tools for building molecular libraries on microelectrode arrays since 2004. Such a library is intriguing because one can take advantage of the library for biological signaling studies. Microelectrode arrays can serve as a powerful platform for those experiments since every electrode in the array can be addressed individually. Unique members of the library targeting biological receptors that one is interested in can be restricted only above unique electrodes in an array. Thus, high-affinity ligands for those receptors can be identified with this strategy. To make this method work, one has to make sure …

Advances In Stereoselective Glycosylation: Electron-Withdrawing Groups, Benzyne-Mediated Stereoinversion, And Visible-Light Photochemistry For 1,2-Cis O-Glycosylation, Erik Giovanni Alvarez Valenzuela

LSU Doctoral Dissertations

The symbiotic relationship between humans and their microbiota is essential for health, with imbalances in the complex microbiota ecosystem linked to a variety of disorders ranging from neurodegenerative to gastrointestinal diseases. Bacteria within the human microbiota, comprising over 1000 known species, are densely and diversely coated with oligosaccharides crucial for functions like cell recognition, communication, signaling, adhesion, proliferation, and pathogenic inhibition. However, studying the structure-activity relationships of these sugars which are also secreted by bacteria is challenging due to difficulties in obtaining homogenous samples from natural sources.

Chemical synthesis offers a solution by enabling the production of well-defined oligosaccharides in …

Antiviral And Cytotoxic Activities And Chemical Profiles Of Two Species Of Abies Nordmanniana From Türkiye, Nazli Sarikahya, Gaye Sümer Okkali, Furkan Ozan Çöven, Sevda Zeinali̇, Gülce Gucur, Ayşe Di̇la Çağlar, Ece Uyar, Ahmet Ceyhan Gören, Ayşe Nalbantsoy

Turkish Journal of Chemistry

Abies is an important genus of the family Pinaceae, with about 50 species found in the highlands of Asia, Europe, North Africa, and North and Central America. The principal aim of the present work was to investigate the chemical content and biological potential of the resin and cone from Abies nordmanniana subsp. bornmulleriana and Abies nordmanniana subsp. equi-trojani, respectively. The flavonoid and phenolic contents of the resin and cones were evaluated using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Additionally, the essential oil and fatty acid compositions were analyzed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID).. Cytotoxicity …

Molecular-Level Studies Of Nanopatterned Biomolecules With Atomic Force Microscopy, Ashley R. Walker

LSU Doctoral Dissertations

Atomic force microscopy (AFM) is an analytical technique in which a tipped probe is gently scanned across the surface in a raster pattern to generate digital images of a sample at the nanoscale. The AFM instrument has three general operational modes, which are contact, non-contact and tapping-mode, that can be used to examine materials at the atomic level. Single-molecular details of biological molecules and other soft organic materials can be captured with minimal denaturation in either ambient or liquid environments when using tapping-mode AFM. In tapping-mode, the probe is driven to oscillate vertically while the tip is scanned across the …

Biotinylated Protein Capture And Tween-20 Assisted Exosome Isolations Via Capillary Chanelled Polymer Fiber, Md Khalid Bin Islam

All Theses

In the past two decades, Marcus and colleagues have led the advancement of capillary-channeled polymer (C-CP) fiber stationary phases for biomacromolecule separations, including proteins and nanovesicles. These stationary phases offer notable advantages, including low cost ($5/column), straightforward column fabrication, and the capacity for on-column surface modification, enabling high chemical selectivity. This study examines a C-CP fiber modification strategy for capturing target proteins and develops a Tween-20-assisted C-CP-based hydrophobic interaction chromatography (HIC) method for the isolation and quantification of exosomes from human urine.

The quest for higher-throughput and cost-effective protein isolation techniques remains a key focus in a variety of end …

Studies Of Oxidopyrylium Ylide Dimers And Their Utility In The Synthesis Of Densely Functionalized Troponoids, Daniel V. Schiavone

Dissertations, Theses, and Capstone Projects

Herein, we describe our efforts to investigate mechanistic considerations of oxidopyrylium ylides and their use in cycloadditions to form complex bicyclic structures and the advancement of these cycloadducts to the synthesis of densely functionalized tropolones. This work also describes applications of tropolones as biologically relevant structures and dynamic fluorophores.

In Chapter 1, we expand upon previous studies done in the Murelli Lab describing the ability of 3-hydroxy-4-pyrone derived oxidopyrylium dimers to revert back to ylides in situ and as result can be used as a clean oxidopyrylium ylide source in accessing oxabicyclic compounds. Intermolecular cycloadditions of these ylides can be …

Development Of Microfluidic Thermal Gel Electrophoresis For Biological Analysis, Mario Ambrocio Cornejo

Wayne State University Dissertations

ABSTRACTDEVELOPMENT OF MICROFLUIDIC THERMAL GEL ELECTROPHORESIS FOR BIOLOGICAL ANALYSIS by MARIO AMBROCIO CORNEJO May 2024 Advisor: Dr. Thomas H. Linz Major: Chemistry (Analytical Chemistry) Degree: Doctor of Philosophy The molecular biology that takes place within cells is vital to the over function of an organism. Healthy cellular function is crucial to a wide web of interconnected processes that need to be balanced and regulated. When these processes become abnormal, disease states are developed. The mapping of biological networks has led to the development of gene therapy and more accurate diagnostic tests. However, there are still vital biomolecules that due to …

Design And Synthesis Of Aminoglycoside-Based Heparan Sulfate Mimetics For Structure-Activity Relationship Studies Of Heparan-Binding Proteins, Joseph Wakpal

Wayne State University Dissertations

Cancer remains a formidable challenge in modern medicine, demanding innovative approaches and treatments. Among the emerging strategies, inhibiting heparanase and fibroblast growth factor 2 (FGF2) has garnered considerable attention in recent years. This dissertation presents a novel approach to designing and synthesizing a diverse library of heparan sulfate (HS) mimetics derived from aminoglycosides to study their binding to two heparin-binding proteins involved in cancer development and metastasis. Heparanase cleaves HS polysaccharide chains in the extracellular matrix (ECM) and is a regulator of aggressive tumor behavior. Clinical studies have illustrated that aberrant heparanase expression correlates with increased tumor size, amplified tumor …

Development Of Small Ligands Targeting Pathogenic Rna Repeats In Neurodegenerative Diseases, Zhihua Chang

Legacy Theses & Dissertations (2009 - 2024)

Pathogenic microsatellite RNA expansions are toxic and can cause neuronal degeneration and dysfunction. Therapeutics that eliminate or neutralize these RNA repeats hold great promise for the treatment of many neurodegenerative diseases because they are uniformly fatal but there is no effective treatment available today. New compounds targeting these pathogenic RNA repeat sequences represent new hope to treat these diseases. The overall goal of my dissertation is to develop a high-throughput screening assay to identify small ligands as potential drug candidates against disease-associated RNA repeats and probe binding mechanisms to guide the design of optimized drug candidates, and eventually validate therapeutic …