Thesis (M.Sc.)--York University, 2004. Graduate Programme in Chemistry. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: LINK NOT YET AVAILABLE.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 156-175).

The synthesis of seventeen novel conformationally constrained analogues of the neurohypophyseal peptide hormone oxytocin is described. Synthesis of the peptides was accomplished using solid-phase synthesis techniques on either Merrifield or p-methyl-benzhydrylamine resin. Cleavage of peptides from the solid support and deprotection were carried out by either ammonolysis followed by treatment with sodium in liquid ammonia or anhydrous HF. Disulfide formation was accomplished by treatment of the deprotected peptide with aqueous potassium ferricyanide. Purification of the peptide analogues involved a combination of either partition and/or size exclusion chromatography followed by reverse-phase high-performance liquid chromatography. Several conformationally constrained unnatural amino acids were incorporated into the synthetic peptides. Two were prepared and incorporated as a mixture of isomers and the resulting peptides were separated and purified by HPLC. The types of analogues prepared fall into three categories: analogues incorporating conformational restrictions in positions 1 and 2; bicyclic oxytocin peptides; oxytocin antagonists with changes at the Asn⁵ residue. The peptides with conformational restrictions at position 1 or 2 are: [Tic²]OT, [DTic²]OT, [DTic²,Thr⁴]OT, [β-MePhe²]OT, [ΔPhe²]OT, [Cys(CH₂)₅¹,Phe²,Thr⁴,Orn⁸]OT and [Pen¹,DPhe²,Thr⁴,Orn⁸]OT. Bicyclic peptide analogues and their monocyclic precursors include: [Mpa¹,Lys⁴,Glu⁵]OT, [Mpa¹,Lys⁴,Glu⁵]OT, [Mpa¹,Glu⁴,Lys⁸]OT, and [Mpa¹,Glu⁴,Lys⁸]OT. Antagonists with changes in the Asn⁵ residue are: [Pen¹,DPhe²,Thr⁴,Thr⁵,Orn⁸]OT; [Pen¹,DPhe²,Thr⁴,Leu⁵,Orn⁸]OT; [Pen¹,DPhe²,Thr⁴,Asp⁵,Orn⁸]OT; and [Pen¹,DPhe²,Thr⁴,Tyr⁵,Orn⁸]OT. Biological assays of these analogues for oxytocic activity in the rat uterus model have shown one of the β-MePhe²-containing peptides, [L-threo-β-MePhe²]OT, to be a very potent agonist and one bicyclic, [Mpa¹,Glu⁴,Lys⁸]OT to be an extremely potent oxytocin antagonist. Initial biophysical investigations employing 250 MHz nuclear magnetic resonance spectroscopy were also undertaken in order to determine possible solution conformations of these peptide analogues.

No description available.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / "May 2003." Typescript. Vita. Includes bibliographical references (leaves 156-175).

No description available.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on July 13, 2010). Vita. Thesis advisor: Carol R. Reinero "May 2010" Includes bibliographical references.

Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / A novel type of supramolecular aggregate, named "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n = 5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer, cholesterol-(K)[subscript n]DEVDGC)₃-trimaleimides, as well as a 1:1 mixture of cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimides form stable nanosponges, whereas cholesterol-(D)[subscript n]DEVDGC)₃-trimaleimide is unable to form supramolecular aggregates by itself. The structure of the novel nanosponges was revealed through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells. Furthermore, the structure of novel binary nanosponges consisting of cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimide units possessing a trigonal maleimide linker, to which either lysine (K)₂₀ or aspartic acid (D)₂₀ are tethered, has been elucidated by means of TEM. A high degree of agreement between these findings and structure predictions through explicit solvent and then coarse-grained molecular dynamics (MD) simulations has been found. Based on the nanosponges’ structure and dynamics, caspase-6 mediated release of the model drug 5(6)-carboxyfluorescein has been demonstrated. Moreover, the binary (DK20) nanosponges have been found virtually non-toxic in cultures of neural progenitor cells. Additionally, DK20 nanosponges were taken up efficiently by leucocytes (WBC) in peripheral blood within 3h of exposure. The percentage of live cells among the WBC was not significantly decreased by the DK20 nanosponges. Therefore, this novel material holds great promise for improved cell-mediated therapy. Two different nanosponges loaded with the anticancer agent perillyl alcohol (POH) were developed to test the suitability of nanosponges for cell-based cancer therapy. Drug-loaded nanoshuttles featuring trigonal supramolecular building blocks, type (D-POH)₁₀K₂₀ and (D-POH)₁₀R₂₀ were synthesized, purified, and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). They were then tested in cell cultures of murine glioma cells (GL26) and murine neural progenitor cells (NPC). The two nanosponges exhibited significantly different biophysical properties (size distribution and zeta potentials). Consequently, different efficacies in killing GL26 and NPC were observed in both, serum free and serum containing culture media. The results from these experiments confirmed that type (D-POH)₁₀K₂₀ nanosponge is an excellent candidate for the cytotherapy of glioblastoma.

Recently, we reported the extraction, purification and amino acid sequence of ansocalcin, the major goose eggshell matrix protein. In vitro studies showed that ansocalcin induces spherical calcite crystal aggregates. We designed two peptides using the unique features of the sequence of ansocalcin and the role of these peptides in CaCO₃ crystallization was investigated. The peptides showed similar activities as compared to ansocalcin, but at a higher concentration. The full characterization of the peptides and a rational for the observed morphology for the calcite crystals are discussed in detail. / Singapore-MIT Alliance (SMA)

Thesis (Ph. D.)--Missouri University of Science and Technology, 2008. / Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed November 4, 2008) Includes bibliographical references.