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Medicinal-Pharmaceutical Chemistry Commons™
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Articles 1 - 11 of 11
Full-Text Articles in Medicinal-Pharmaceutical Chemistry
Polymer-Based Nanotherapeutics To Combat Difficult-To-Treat Bacterial Infections, Jessa Marie V. Makabenta
Polymer-Based Nanotherapeutics To Combat Difficult-To-Treat Bacterial Infections, Jessa Marie V. Makabenta
Doctoral Dissertations
The continuous emergence and spread of antibiotic-resistant bacteria are a global health emergency, debilitating the capability to prevent and cure various infectious diseases that were once treatable. Antibiotic therapy is further rendered ineffective due to biofilm formation and the ability of bacteria to thrive and colonize inside mammalian cells. Given the diminishing efficacy of available antibiotics combined with the scarcity of new therapeutics entering the antibiotic pipeline, innovative treatment strategies are urgently in demand. Nanomaterial-based strategies offer ‘outside of the box’ approach for the treatment of antibiotic-resistant bacterial infections. Nanomaterials feature tunable physicochemical properties that can be carefully modified to …
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Doctoral Dissertations
The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Doctoral Dissertations
Advancing pharmaceutical technology has made it possible to treat diseases once considered ‘undruggable.’ Access to these new pharmaceutical targets is possible thanks to the advent of protein and nucleic acid therapeutics. Responses to the COVID-19 pandemic, as well as cutting-edge treatments for cancer and multiple sclerosis have centered on these biologic therapies, promising even greater value in the future. However, their utility is limited at a cellular level by inability to cross the plasma membrane. Nanocarrier technologies encapsulate therapeutics and facilitate uptake into the cell but are often trapped and degraded in endosomes. Arginine-functionalized gold nanoparticles (Arg-NPs) provide efficient, direct …
Chemical Manipulation Of Macrophages: Nanomaterial And Molecular Approaches, Joseph Hardie
Chemical Manipulation Of Macrophages: Nanomaterial And Molecular Approaches, Joseph Hardie
Doctoral Dissertations
Macrophages, phagocytic cells of the innate immune system, are the body’s first line of defense against pathogens and are responsible for tissue maintenance. Macrophages are capable of sensing and internalizing external stimuli, and in response change their morphology and phenotype accordingly. Because macrophages are integral to immune function and tissue maintenance, dysregulation of macrophage behavior is associated with a range of diseases including infections, cancer, autoimmune disorders, atherosclerosis, and more. Because of the implications of macrophage failure, there is interest in creating new materials to manipulate macrophage behavior for a therapeutic effect. In this thesis, I describe the application of …
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Doctoral Dissertations
Background: Nectar and pollen are rich in phytochemicals, some of which can reduce disease in pollinators, including agriculturally important honey and bumble bees. Floral phytochemicals could influence the ecological and evolutionary relationships between plants, their pollinators, and parasites that cause pollinator disease. Antiparasitic effects of phytochemicals could be exploited to ameliorate pollinator disease and decline, and thereby sustain pollinator-dependent agricultural production. However, prior studies showed variable effects of phytochemicals on infection in live bees, where differences in bee genotype, abiotic conditions, and parasite strain could influence results. Approach: I used cell cultures of the intestinal trypanosome parasite of bumble bees, …
Nanoparticle As Supramolecular Platform For Delivery And Bioorthogonal Catalysis, Gulen Yesilbag Tonga
Nanoparticle As Supramolecular Platform For Delivery And Bioorthogonal Catalysis, Gulen Yesilbag Tonga
Doctoral Dissertations
Nanoparticles (NPs) are being investigated widely for many applications including imaging, drug delivery, therapeutics, materials, and catalysis due to their unique and tunable physical and chemical properties. Among NPs, gold nanoparticles (AuNPs) have attracted great attention due to ease of synthesis and surface functionalization, inertness of the core, biocompatibility, and functional versatility. Introducing supramolecular chemistry into the nanoparticle-based platforms brings out controllable properties, dynamic self assembly processes, and adjustable performance. My research has focused on the synthesis of AuNPs bearing different surface functionalities and their host-guest interactions with synthetic small molecules or commercially available hydrophobic catalysts for delivery and therapeutic …
Analytical Methods To Support Design And Optimization Of Protein Drug Conjugate: Focusing On Haptoglobin-Hemoglobin Complex As A Drug Carrier, Shengsheng Xu
Doctoral Dissertations
Acquired immunodeficiency syndrome (AIDS) remains one of the most serious public health challenges and a significant cause of mortality for certain populations. Despite the large number of antiretrovirals (mostly nucleotide and nucleoside analogs) developed in the past two decades, the inability of small molecule therapeutics to target HIV reservoirs directly creates a significant obstacle to their effective utilization. Indeed, achieving the desired therapeutic effect in the absence of the effective targeted delivery must rely on dosage escalation, which frequently causes severe toxicity. This problem may be solved by conjugation of antiretroviral agents to endogenous proteins (e.g., hemoglobin haptoglobin complex) that …
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Doctoral Dissertations
The design and synthesis of responsive supramolecular assemblies are of great interest due to their applications in a variety of areas such as drug delivery and sensing. We have developed a facile method to prepare self-crosslinking disulfide-based nanogels derived from an amphiphilic random copolymer containing a hydrophilic oligo-(ethylene glycol)-based side-chain functionality and a hydrophobic pyridyl disulfide functional group. This thesis first provides a concept of studying the influence of Hofmeister ions on the size and guest encapsulation stability of a polymeric nanogel. The size and core density of nanogel can be fine-tuned through the addition of both chaotropes and kosmotropes …
Design, Synthesis, And Bio Relevant Applications Of Zwitterionic Amphiphilic Macromolecular Assemblies, Rajasekhar Reddy Rami Reddy
Design, Synthesis, And Bio Relevant Applications Of Zwitterionic Amphiphilic Macromolecular Assemblies, Rajasekhar Reddy Rami Reddy
Doctoral Dissertations
Supramolecular nanoassemblies capable of reducing non-specific interactions with biological macromolecules, such as proteins, are of great importance for various biological applications especially for targeted drug delivery therapeutics. Recently, zwitterionic materials have been shown to reduce non-specific interactions with biomolecules, owing both to their charge neutrality and their ability to form strong hydration layer around zwitterions via electrostatic interactions. This dissertation focuses on design, synthesis, thorough characterization, and applications of zwitterionic amphiphilic dendrimers and polymeric materials. Firstly, A new triazole-based zwitterionic moiety was conceived and incorporated as the hydrophilic functionality in facially amphiphilic dendrons. Self-assembly characteristics and the structural and functional …
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Doctoral Dissertations
Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …
Pharmacological Chaperoning In Fabry Disease, Jerome Rogich
Pharmacological Chaperoning In Fabry Disease, Jerome Rogich
Masters Theses 1911 - February 2014
Fabry Disease is an X-‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-‐ Galactosidase A (α-GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. …