No description available.

Thesis (doctoral)--Friedrichs-Universität Halle-Wittenberg, 1912. / Vita. Includes bibliographical references (p. [74]-86).

Aromatic oligoamide foldamers has high potential to mimic the secondary structures of biopolymers. These oligomers by using intramolecular hydrogen bonds and £k-£k interaction of aromatic rings to form a stable foldamer. We use the helical form of these oligomers and combine to the groove binding agents, then study the influence on DNA .

Peptides are short, sequence and length specific oligomers composed of small amino acid residues. Nature has refined these peptide sequences and their endogenous function through evolution. In addition, peptides have played an important role in medicine, which has lead to further research into developing peptides as lead pharmaceuticals (therapeutic peptides). Unfortunately, therapeutic peptides are inferior as drug candidates due to their low oral bioavailability; immunogenicity and potential to be attacked by peptidases. Fortunately, peptides can be modified by steric constraints, cyclization, and/or replacement of the peptide backbone itself creating a mimic (peptidomimetic) of the original peptide. Peptidomimetics are deliberately designed to have increased protease resistance, reduced immunogenicity and improved bioavailability when compared to the original endogenous peptide. One such peptide, Magainin is a O One such peptide, Magainin is a well-studied, a-helical peptide found in African clawed frogs. This peptide has antibiotic properties (against pathogenic bacteria), which partly arises from the hydrophilic portion of the peptide having basic amino acid side chains periodically disposed on one side of the a-helix. This property of magainin causes its attraction to negatively charged bacteria cell membranes. Unfortunately, as in the case of other antibiotics, pathogenic bacteria have developed effective countermeasures against magainin. We designed a peptidomimetic based on magainin and implemented a plan to determine what type of molecules could be assembled for a magainin mimic. We successfully utilized molecular modeling (Monte Carlo conformational search), as well as results from previous experiments to elucidate what type of molecules, as well as how many molecules would be necessary to create a novel helical-like magainin peptidomimetic. It was discovered that C2 symmetric diamines would be best at generating the helical-like motif and the amino acid lysine to generate the basic side chain. The next step was the successful connection of two C2 symmetric molecules via a urea linkage and then one more connection to a lysine (a-amino group) residue, creating a short sequence of oligoureas (trimers). Finally, attempts to connect the oligoureas trimers were attempted using a solid-phase synthesis approach to generate a functional magainin mimic.

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Orientador: Elias Basile Tambourgi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-04T13:54:52Z (GMT). No. of bitstreams: 1 Barbosa_EduardoJose_M.pdf: 1801283 bytes, checksum: e7ae140b96b1e6af3f8cf78035307f33 (MD5) Previous issue date: 2004 / Resumo: O objetivo deste trabalho é desenvolver uma metodologia de cálculo, de uso simples, porém de caráter robusto, a ser utilizado na seleção de sistemas de agitação e mistura, que englobam: Cálculo/dimensionamento do eixo do agitador para torção e flexão tipo "eixo vazado" para conjunto único e de múltiplos impelidores; Verificação da Rotação Crítica para sistemas de agitação que possuem eixos em balanço; Estimar a potência consumi da em sistemas agitados que utilizam impelidor( es) para produtos com viscosidades variadas. O programa computacional é estruturado a partir do levantamento de equações pertinentes aos sistemas estudados bem como é fruto de experiências já consolidadas em aplicações práticas (industriais) onde o mesmo pode ser utilizado no desenvolvimento e fabricação de tanques, vasos, reatores e sistemas de agitação. O programa desenvolvido, em ambiente Excel pode ser utilizado em substituição aos softwares comerciais, de elevado custo de aquisição e atualização. As proporções recomendadas para uma melhor eficiência do sistema de agitação e mistura, como por exemplo, a altura de líquido x diâmetro do vaso, serão abordadas aqui, bem como a verificação da mudança do comportamento da agitação influenciados pela variação da geometria do tanque e do impelidor e da viscosidade (características do fluído) no processamento no qual eles estão inseridos / Abstract: The objective of this work is to present a calculation methodology, of simple use, however a efficient form to design and to be used on mixing systems selection that comprise: Agitator hollow shaft design/calculation for bending and torsion for single and multiple impellers conditions; Check and compute Critical Speeds in Agitated Vessels that have overhung shafts. Estimating power consumption by impellers on mixing of products with several viscosities; The computational tool was based on several research, as well is a result of the experiences yet consolidated on industrial real applications where it is used to design agitated vessels, tanks, reactors and agitation systems. Computer method run in Excel and can be used on substitution of commercial programs that have high acquisition and up-date prices. Recommended dimensions, for example, how the level of liquid x vessel diameter modify the agitation efficiency, will be treated here, then also, will see the modification on mixing performance by influence varying geometry (impeller and tank) and the viscosity (fluid characteristics) on processes were are involved. / Mestrado / Sistemas de Processos Quimicos e Informatica / Mestre em Engenharia Química

Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / A series of chiral symmetrical and unsymmetrical acid-functionalized Schiff-base ligands were synthesized by condensation reactions between 3-formyl salicylic acid and the two diamines (1R,2R)-cyclohexyldiamine (CHDA) and (R)-[1,1'-binapthalene]-2,2'-diamine (BINAM). The addition of a weak base (TEA) to these Schiff-bases resulted in the formation of a partially deprotonated ligand while the addition of the strong base NaOMe, resulted in fully deprotonated ligands. Complexations were carried out using metal salts of Fe(II), Co(II), Ni(II), Cu(II), Cu(I) and Zn(II). The partially deprotonated unsymmetrical Schiff-base (CHDA as the backbone), resulted almost exclusively in the formation of double-stranded helices with M helices. The fully deprotonated ligand, on the other hand, formed cubane-type structures with Fe(II), Co(II) and Ni(II) in methanol. Similar cubane-type structures were also obtained after complexation of the symmetrical CHDA-based ligands with Fe(II) and Co(II) using NaOMe in methanol. Reactions involving Cu(II) and Cu(I) salts resulted in either mono-or dinuclear salen complexes, even if the unsymmetrical Schiff-base was used as the starting ligand. This type of ligand conversion is dependent of the metal salt concentration in the reaction. Unsymmetrical Schiff-base ligands have a higher tendency to undergo conversion to their symmetrical salen analogues if the metal salt is added is much excess.

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Design of complex protein folds requires complete understanding of the stereochemical principles that govern polypeptide chain folding. Extensive studies on design and synthesis of specific secondary structures like β-helices, β -sheets and hairpins have taught us that the unnatural amino acid aminoisobutyric acid (Aib) can be successfully employed for helix nucleation and tight turns of appropriate stereochemistry are facilitated by the use of DPro-Xxx sequences. Availability of such rigid secondary structure scaffolds therefore permits the design of synthetic peptides that can be used as models for investigation of tertiary interactions, primarily that of aromatic residues. Chapter 1 summarizes the present knowledge of peptide design using non-protein amino acids. The chapter also details the unique features of aromatic amino acids, especially tryptophan, and their employment as secondary structure stabilizing elements. Chapters 2-7 contain detailed descriptions of the work carried out on design, synthesis, and structural characterization of designed peptides containing aromatic amino acids. In Chapter 2, the use of aromatic pairs in strand segments of peptide hairpins has been discussed with the results clearly indicating that aromatic interactions at the non-hydrogen bonding position of peptide hairpins contribute to structure stability. In Chapter 3, accommodation of the Leu-Trp-Val segment in helical scaffolds the role of Trp residues in crystallization has been discussed. Chapter 4 outlines the influence of a large number of Trp residues on the preferred backbone conformation, with the studies clearly indicating a preference for helical scaffolds in small peptides. The role of Trp residues at turn regions of peptide hairpins has been discussed in Chapter 5, using examples from both synthetic peptides and from natural peptides containing Pro-Trp segments. The studies suggest that the Pro-Trp segments serve as helix nucleators and disrupt formation of peptide hairpins. The results of this study have been further extended to Conus monile peptides, discussed in Chapter 6. The studies also suggest the role of an aromatic-Pro segment on the cis-trans isomerization of the Xxx-Pro tertiary amide unit. Chapter 7 discusses the contribution of a Cys-His vs Tyr-His pair on strand segment stability in diproline nucleated peptide hairpins. Chapter 8 summarizes the key findings of the work. Chapter 9 lists the references cited in the thesis and the Appendix chapter provides details of experimental techniques used in the study.β

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