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Pharmaceutical Sciences (PhD) Dissertations

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Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao Jan 2026

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …

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Mechanistic Study Of Antimicrobial Cyclic Peptide [R4w4] Antibacterial Effectiveness Against Methicillin-Resistant Staphylococcus Aureus (Mrsa), Ajayi Akinwale May 2024

Mechanistic Study Of Antimicrobial Cyclic Peptide [R4w4] Antibacterial Effectiveness Against Methicillin-Resistant Staphylococcus Aureus (Mrsa), Ajayi Akinwale

Pharmaceutical Sciences (PhD) Dissertations

Antimicrobial peptides (AMPs) are being explored as a potential solution to combat antibiotic resistance, as they have shown promise in reducing susceptibility to antibiotics. This study explores if [R4W4] peptide is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluates synergism of gentamicin and [R4W4] against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) by checkered board assay. The MRSA resistant to [R4W4] and possibility with other antibiotics was evaluated with serial passage. Moreover, we investigated the mechanism of action of [R4W4 …

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Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali May 2023

Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali

Pharmaceutical Sciences (PhD) Dissertations

The Ca2+-activated potassium channels KCa channels are a unique family of potassium channels activated by intracellular calcium. KCa channels are critical for maintaining K+ homeostasis and modulate several physiological processes, from the firing properties of neurons to the control of the transmitter release. The Ca2+ sensitivity of these channels allows intracellular Ca2+ to regulate the electrical activity of the cell membrane. Increased Ca2+ sensitivity of KCa channels caused by gain of function mutations (GOF) in the KCNN genes results in a broad spectrum of human channelopathies, including Zimmermann- Laband syndrome (ZLS), …

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Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong May 2022

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system 12-14. Our …

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Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei Aug 2021

Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei

Pharmaceutical Sciences (PhD) Dissertations

The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH2-CWxEAAYQrFL-CONH2) with high proteolytic stability and specificity for breast cancer cells was reacted with …

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Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari Dec 2019

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R5K]W5, [R6K]W5, [R5K]W6, [R7K]W5, [R5K]W7, [R6K]W6, and [R7K]W7 were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

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