No description available.

Thesis (M.S.)--Rochester Institute of Technology, 1992. / Typescript. Includes bibliographical references (leaves 95-97).

Thesis (Ph. D.)--Carleton University, 1992. / Also available in electronic format on the Internet.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1964. / Abstracted in Dissertation abstracts, v. 25 (1965) no. 7, p. 3831-2. Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--Drexel University, 2006. / Includes abstract and vita. Includes bibliographical references (leaves 308-309).

In this study we have used isothermal titration calorimetry, ITC, and circular dichroism spectropolarimetry, CD, to directly measure the thermodynamics and the structural changes for binding histones, H11 and H14, to DNA. The ITC data have been used to estimate the binding constant, (K ≈ 108) and the enthalpy change (ΔH ≈ + 5 (H11 at 25ºC), ΔH ≈ +20 kcal/mol (H14 at 15 ºC) for formation of the H1/DNA complex. CD data indicate that both H1 and DNA are partially unfolded in the H1/DNA complex. Protein and DNA unfolding must contribute to the large unfavorable endothermic enthalpy change for complex formation. The ITC data indicate that the H11 binding site is comprised 30 DNA base pairs while H14 interacts with approximately 36 DNA base pairs. At saturation, our data are consistent with 100% of the H1 binding sites being occupied in the H1/DNA complex.

No description available.

The structural requirements for the binding of dynorphin to the kappa opioid receptor are of profound clinical interest in the search for a powerful non-addictive analgesic. These requirements are thought to be met by the membrane-mediated conformation of the opioid peptide dynorphin A-(1-13}, Tyr¹-Gly²-Gly³-Phe⁴-Leu⁵-Arg⁶-Arg⁷-Ile⁸-Arg⁹-Pro¹⁰-Lys¹¹-Leu¹²-Lys¹³. Schwyzer [𝘉𝘪𝘰𝘤𝘩𝘦𝘮𝘪𝘴𝘵𝘳𝘺 25: 4281-4286 (1986)] has proposed an essentially α-helical membrane-mediated conformation of the tridecapeptide. In the present study, the hydrophobic moment, the helix probability and a four -state secondary structure prediction were computed. They signified, in agreement with circular dichroism (CD) studies on phospholipid-bound dynorphin A-(1-13)-tridecapeptide, negligible helical content of the peptide. CD studies demonstrated that the aqueous-membraneous interphase can be mimicked by methanol. The 500 and 620 MHz ¹H nuclear magnetic resonance (NMR) spectra of dynorphin A-(1-13) in methanolic solution were sequence-specifically assigned with the aid of correlated spectroscopy (COSY), double-quantum filtered phase-sensitive COSY, relayed COSY (RELAY) and nuclear Overhauser enhancement spectroscopy (NOESY). 2-D CAMELSPIN/ROESY experiments indicated that at least the part of the molecule from Arg⁷ to Arg⁹ was in an extended or β-strand conformation, which was in line with deuterium exchange and temperature dependence studies of the amide protons. ¹³C_α spin-lattice relaxation rate constants indicated a non-rigid backbone conformation. Transferred nuclear Overhauser effect studies on aqueous systems containing dynorphin A-(1-13) in the presence of dimyristoyl-phosphatidylcholine bilayers indicated a folded conformation from Tyr¹ to Leu⁵. The findings were incorporated into a tentative molecular model, which also indicated a non-helical, non-extended conformation for the rest of the molecule in the presence of corresponding distance-restrained negative charges. / Thesis / Master of Science (MSc)

Made available in DSpace on 2014-06-11T19:31:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-08-19Bitstream added on 2014-06-13T20:21:35Z : No. of bitstreams: 1 vicente_ef_dr_araiq_parcial.pdf: 165362 bytes, checksum: 96b2cf2b3ae74363a4b5898b957a3b6a (MD5) Bitstreams deleted on 2015-06-03T11:42:42Z: vicente_ef_dr_araiq_parcial.pdf,. Added 1 bitstream(s) on 2015-06-03T11:44:08Z : No. of bitstreams: 1 000721605_20150819.pdf: 147542 bytes, checksum: f5cc64495e4f5a562a1e11d2ae711ce3 (MD5) Bitstreams deleted on 2015-08-20T11:58:40Z: 000721605_20150819.pdf,. Added 1 bitstream(s) on 2015-08-20T11:59:13Z : No. of bitstreams: 1 000721605.pdf: 4723399 bytes, checksum: 29bea79ab4fbb0c39fdce178c6b55872 (MD5) / A diidroorotato desidrogenase é uma enzima que apresenta um papel central na biossíntese de pirimidinas e catalisa a oxidação do diidroorotato a orotato. A enzima atua durante a via “de novo” de síntese de pirimidinas e está presente em quase todos os organismos vivos. A diidroorotato desidrogenase humana (HsDHODH) pode representar um importante alvo para o tratamento de doenças hiperproliferativas e inflamatórias, já que sua inibição bloqueia a síntese de ácidos nucléicos, impedindo a sua proliferação. Esta enzima tem uma estrutura monomérica e está associada com a membrana interna das mitocôndrias pela sua extensão N-terminal. Assim, entender em detalhes como esta enzima interage com a membrana poderia elucidar um alvo seletivo para drogas antiproliferativas, antiparasíticas e imunossupressivas. Esta região está também envolvida com a catálise central da enzima, sequestrando moléculas de ubiquinona presentes na membrana, fundamentais para as reações de oxirredução feitas pela enzima. Deste modo, para um melhor entendimento destes aspectos, neste trabalho foram sintetizados, por meio da Síntese de Peptídeos em Fase Sólida (SPFS) o peptídeo Ac-GDERFYAEHLMPTLQGLLDPESAHRLAVRFTSLG-NH2, que corresponde ao microdomínio existente na porção N-terminal da HsDHODH, entre os resíduos 33 e 66. Três análogos marcados com o aminoácido paramagnético TOAC nas posições 0, 12 ou 20, além de dois análogos duplamente marcados também foram obtidos. Ambos os peptídeos com dupla marcação possuem uma cisteína ligada ao spin MTSSL na posição 35 (C-terminal) se diferenciando pela posição do segundo marcador: um contendo outra cisteína ligada ao MTSSL na posição 12 e o segundo possuindo o TOAC na posição 0 (ou N-terminal). Estes peptídeos foram estudados por técnicas... / The dihydroorotate dehydrogenase is an enzyme that has a central role on the pyrimidine biosynthesis and catalyses the oxidation of dihydrorotate to orotate. The enzyme acts on de novo pyrimidines nucleotides pathway and it is present in almost all the live organisms. The human dihydroorotate dehydrogenase (HsDHODH) can represent an important target for the treatment of hiperproliferative and inflammatory diseases, since its inhibition blocks the nucleic acid synthesis, which restrains the cell proliferation. This enzyme has a monomeric structure and it is associated into the inner mitochondrial membrane by the N-terminal extension. Thus, understanding in details how this enzyme interacts with the membrane could help to elucidate a selective target for antiproliferative, antineoplasic and immunosuppressive drugs. This region is also involved with the central enzyme catalysis, harboring quinones molecules that are in the membranes, which is essential for the oxidation-reduction reactions made by the HsDHODH. In this way, for a better evaluation of these aspects, in this work we synthesized through the Solid Phase Peptide Synthesis (SPPS) the peptide Ac-GDERFYAEHLMPTLQGLLDPESAHRLAVRFTSLG-NH2, which corresponds to the HsDHODH N-terminal microdomain, between the residues 33 to 66. Three analogues labeled with the paramagnetic amino acid TOAC in the positions 0, 12 or 20 and two doubly labeled analogues were also synthesized. Both doubly labeled peptides contain a MTSSL-attached cysteine residue bounded to the position 35 (C-terminus), differing by the position of the second spin label: one possessing a cysteine with MTSSL at position 12 and the other contains TOAC at position 0 (N-terminus). These peptides were studied by spectroscopy techniques in order to obtain information about... (Complete abstract click electronic access below)

Linear dichroism in Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy has been used to determine molecular orientation at surfaces and in microscopic domains. However, the molecular orientation of n-alkanes cannot be derived unambiguously from their NEXAFS spectra due to the inadequate understanding of the character of the relevant spectroscopic features in the NEXAFS spectra of n-alkanes (i.e. C 1s to sigma*C-H, C 1s to sigma*C-C transitions).<p>We have studied the linear dichroism in the NEXAFS spectra of n-alkane thin films by using angular dependent NEXAFS spectroscopy to explore the molecular orientation of hexacontane (HC, n-C60H122). The HC thin films were epitaxially grown onto the cleaved NaCl (001) surfaces by physical vapor deposition. NEXAFS spectra of the HC thin film were acquired at different angles using STXM microscopy. A detailed analysis of the angular dependence of the NEXAFS spectra of the HC thin film helps to understand the relationship between the linear dichroism and the molecular orientation in n-alkane molecules. This linear dichroism in the NEXAFS spectroscopy of n-alkanes is relevant for quantitative measurements of molecular orientation, such as for the microanalysis of crystalline organic materials. <p>The linear dichroism of the NEXAFS resonances for n-alkanes has also been studied by ab initio calculations. These calculations were carried out on an isolated n-alkane molecule and a cluster of n-alkane molecules. The calculations on an isolated n-alkane molecule are used to study the linear dichroism for the NEXAFS resonances above the C 1s IP. The cluster calculations account for matrix effects in the NEXAFS features of condensed n-alkanes. A comparison of calculations on an isolated molecule and on a cluster of molecules provides information on how the NEXAFS spectra change from gas phase to condensed phase and determines the linear dichroism of each NEXAFS feature below the C 1s IP.<p>In the process of preparing n-alkane thin films for the study of linear dichroism, the morphology and molecular orientation of n-alkane thin films with different chain length (n-C36H74 and n-C60H122) have also been investigated by the NEXAFS spectroscopy and microscopy. These thin films were epitaxially grown onto cleaved NaCl (001) surfaces by physical vapor deposition. The results revealed that the morphology and molecular orientation of n-alkane thin films depend on the chain length and deposition parameters, such as substrate temperature. These observations have been rationalized by the thermodynamics of nucleation and the kinetics of growth.