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Pharmaceutical Chemistry Dissertations and Theses: Recent submissions
Now showing items 41-60 of 141
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SITE-SPECIFIC GLYCOSYLATION ANALYSIS OF IgG3 AND THE EFFECT OF GLYCOSYLATION ON THE STRUCTURE, PHYSICAL STABILITY AND Fc RECEPTOR INTERACTIONS OF IgG3 Fc
(University of Kansas, 2017-08-31)Therapeutic monoclonal antibodies based on the IgG class of antibodies are glycoproteins that contain glycosylation sites within their Fc region. Glycosylation is important for Fc-mediated effector functions such as Antibody ... -
Design of Novel Antigen-Specific Immunotherapies for the Treatment of Autoimmune Disorders
(University of Kansas, 2017-08-31)Autoimmune disorders are a challenging problem for both afflicted patients and pharmaceutical scientists, since they involve one of the most complex biological systems – the immune system. A dysregulation of antigen ... -
Comparative Evaluation of Well-Defined IgG1 Fc Glycoforms as a Model System for Biosimilar Comparability Analysis
(University of Kansas, 2017-08-31)The patents of several best-selling biologic therapeutic products are expiring soon. Consequently, the interest of developing biosimilar products is growing. A biosimilar product is developed if there are no clinically ... -
ELUCIDATION OF THE IMPACT OF N-GLYCAN STRUCTURE ON PHYSICAL STABILITY AND LOCAL FLEXIBILITY OF WELL-DEFINED IgG1-Fc GLYCOFORMS FROM A PHARMACEUTICAL DEVELOPMENT PERSPECTIVE
(University of Kansas, 2017-08-31)Therapeutic efficacies of IgG monoclonal antibodies (mAbs) depend on their physicochemical structural integrity, stability, flexibility and biological functionality. IgG-Fc glycosylation at Asn-297 is important for the ... -
Development of Biologics Using the claMP Tag: Influence of the claMP Tag on Half-life and Proteolytic Stability
(University of Kansas, 2017-08-31)Peptide and protein therapeutics encounter proteases at every stage of delivery, beginning at the site of administration and ending in the intracellular lysosomal compartment. An intact, stable molecule is desired upon ... -
Modifying the Fc Asn297 Glycan of Human IgG2 Subclass for Improved Antibody Therapeutics and Design of Site-Specific Antibody Drug Conjugates
(University of Kansas, 2017-08-31)Immunoglobulin G (IgG) is a complex glycoprotein that is largely being used in the development of antibody-based therapeutics to treat a variety of diseases such as cancers, autoimmune diseases, and infectious diseases. A ... -
Towards a greater mechanistic understanding of reversible protein-protein interactions and irreversible aggregation of IgG1 monoclonal antibodies
(University of Kansas, 2016-08-31)Immunoglobulin G1 monoclonal antibodies (IgG1-mAbs) are one of the most important and fastest growing class of biotherapeutic agents. These mAbs are being used to treat a wide range of medical conditions such as cancer, ... -
Quantitative methods to elucidate and characterize various aggregation pathways of an IgG1 monoclonal antibody
(University of Kansas, 2016-05-31)The term protein aggregation is used in pharmaceutical biotechnology literature to describe a collection of different mechanisms that produce non-native, net irreversibly associated protein molecules. The presence of protein ... -
Novel Cys crosslinks and Trp side chain cleavages in proteins and peptides exposed to light
(University of Kansas, 2015-05-31)Protein pharmaceuticals, like monoclonal antibodies (mAbs), are sensitive to many degradation pathways, such as oxidation and photodegradation. Photostability testing provides essential information to characterize protein ... -
Co-Delivery of Immunomodulators and Autoantigen as Antigen-Specific Immunotherapy for the Treatment of a Murine Model of Multiple Sclerosis
(University of Kansas, 2016-12-31)Multiple Sclerosis (MS) is an autoimmune disease characterized by the breakdown of immune tolerance towards autoantigen in the myelin sheath surrounding the neurons. Current therapies for MS and other autoimmune diseases ... -
Engineered Nanomaterials for Targeted Imaging and Therapy
(University of Kansas, 2015-05-31)The early diagnosis of cancer can help direct the best treatment strategy and improve patients' survival. The unique and tunable properties of nanoparticles facilitate the development of diagnostic imaging tools for earlier ... -
The Development of Capillary and Microchip Electrophoresis Methods for the Analysis of Pharmaceuticals in Developing Countries
(University of Kansas, 2014-08-31)Maintaining a consistent supply of pharmaceuticals to developing countries could save millions of lives per year. One of the major roadblocks in this effort is an abundance of substandard and counterfeit drugs in the supply ... -
Mechanism of Degradation of an alpha- Keto-Epoxide, PIV-PR-020: A Model for the Warhead for Various Proteasome Inhibitor Anticancer Agents
(University of Kansas, 2015-05-31)Proteasome inhibitors are clinically effective treatment of multiple myeloma and mantle cell lymphoma. One proteasome inhibitor already on the market and one under clinical investigation are epoxy-ketones that potently and ... -
The reaction pathways of hydrogen peroxide in the presence of scavengers and its transition metal catalyzed oxidation of disulfide bridge containing peptides
(University of Kansas, 2015-05-31)The degradation pathway of hydrogen peroxide (H2O2) with sodium pyruvate elucidates the formation and breakdown of an intermediate formed during the reaction. Sodium pyruvate is a potential base for the creation of a ... -
Inhibition of Cell Adhesion by Peptides Derived from the EC-4 Domain of E-Cadherin
(University of Kansas, 2015-08-31)The objective of this project was to evaluate the biological activity of peptides derived from the EC-4 domain of E-cadherin in inhibiting E-cadherin-mediated cell-cell adhesion. The activity of these peptides was determined ... -
Delivering Molecules to the Brain using Blood-Brain Barrier Modulators: Mechanism of Action and Activity of Cyclic and Linear Peptides from E-cadherin
(University of Kansas, 2015-12-31)Delivering Molecules to the Brain using Blood-Brain Barrier Modulators: Mechanism of Action and Activity of Cyclic and Linear Peptides from E-cadherin Ahmed L. Alaofi The University of Kansas, 2015 The goals of this work ... -
Role of Glycosylation of IL-1ra on its Binding to IL-1R1
(University of Kansas, 2015-12-31)Interleukin 1 (IL-1) is an inflammatory cytokine that helps the immune system fight disease. The inflammatory action of IL-1 is regulated by the naturally occurring interleukin 1 receptor antagonist (IL-1ra). IL-1ra contains ... -
Engineering Particles and Polymers to Improve Pulmonary Therapeutics
(University of Kansas, 2015-12-31)Pulmonary drug delivery has been an underutilized delivery space. Classically, pulmonary delivery has been employed for local delivery of small molecules for lung-centric respiratory diseases. The most typical example has ... -
pH and Conformation Modulate Copper-Mediated Site-Specific Degradation of the IgG1 Hinge Region
(University of Kansas, 2015-12-31)Fragmentation in the hinge region of an IgG1 monoclonal antibody (mAb) can impact product stability, potentially causing changes in potency and efficacy. Metals ions, such as Cu2+, can bind to the mAb and undergo hydrolysis ... -
Understanding Therapeutic Monoclonal Antibody Aggregation Mechanisms through Biophysical, Biochemical and Biological Characterization of Two Types of Immunoglobulin G Dimers
(University of Kansas, 2015-12-31)Aggregation has been identified as one of the major degradation pathways that affect the quality and efficacy of protein therapeutics. Dimers are one of the predominant oligomeric species found in monoclonal antibody (mAb) ...