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Full-Text Articles in Medicinal and Pharmaceutical Chemistry
Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali
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), …
Amphiphilic Cyclic Cell-Penetrating Peptides Containing Tryptophan And Arginine As Anticancer Agents And Drug Delivery System, Khalid Zoghebi
Amphiphilic Cyclic Cell-Penetrating Peptides Containing Tryptophan And Arginine As Anticancer Agents And Drug Delivery System, Khalid Zoghebi
Pharmaceutical Sciences (PhD) Dissertations
Amphiphilic cyclic cell-penetrating peptides composed of an increasing number of alternative tryptophan (W) and arginine (R) were synthesized and evaluated as a molecular transporter and for their ability to deliver doxorubicin (Dox) and large molecular weight molecules, such as siRNA and proteins. We prepared a cyclic peptide containing alternative tryptophan (W) and arginine (R) residues and a lysine containing a free side chain amino group. Cyclic peptide [(WR)8WK βA] was conjugated through the free side chain amino group of β-alanine with Dox via a glutarate linker to afford [(WR)8WK]bA-Dox conjugate. The conjugate inhibited the cell viability of ovarian adenocarcinoma (SK-OV-3) …
Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi
Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi
Pharmaceutical Sciences (PhD) Dissertations
Triple-negative breast cancer (TNBC) is the most aggressive and difficult to treat subtype of breast cancer. Chemotherapy is an active treatment option in combination with other treatments; however, the side effects limit the effective therapeutic dose. To selectively target the cancer cells, I have synthesized three peptide-drug conjugates (PDCs) to specifically target the TNBC cells. The first PDC contains peptide 18-4 with an additional cysteine in the N-terminal (NH2- CWxEAAYQrFL-CONH2) linked to aldoxorubicin (Aldox), a modified version of a common chemotherapy drug doxorubicin (Dox). The cytotoxicity of the PDC and free Dox (positive control) were assessed against MDA-MB-231, MDA-MB-468, and …
Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei
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 …
Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari
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 …