Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 472-488). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 472-488). Also available on the Internet.

Thesis (Ph. D.)--Florida State University, 2002. / Advisor: Dr. James G. Skofronick, Florida State University, College of Arts and Sciences, Dept. of Physics. Title and description from dissertation home page (viewed Oct. 3, 2003). Includes bibliographical references.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Haskell W. Beckham; Committee Co-Chair: David Bucknall; Committee Member: Andrew Lyon; Committee Member: Jiri Janata; Committee Member: Lawrence Bottomley; Committee Member: Mohan Srinivasarao. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 193-199). Available also in a digital version from Dissertation Abstracts.

The binding between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak is one of the key protein-protein interactions in the regulation of programmed cell death (apoptosis). Since it is well recognized that the BH3 domain of Bak adopts an amphipathic α-helix to interact with Bcl-xL through hydrophobic and electrostatic effects, conformational studies and possible applications of the α-aminoxy acid-containing peptides as mimics of the α-helix of Bak BH3 domain have been carried out. The main results are summarized below. Four short peptides ZT1?ZT4 containing alternating α-aminoxy acids/α-amino acids as the mimics of the α-helix of Bak protein were designed and synthesized. However, none of these four peptides, at the concentration of 25 μM, exhibited a significant inhibitory effect on the Bcl-xL inhibition test. Circular dichroism spectroscopic studies on ZT1?ZT4 as well as short model peptides N-minus, N-plus, C-minus and C-plus suggest that the proposed secondary structure, the 7/8 helix, is not stable in aqueous solutions. 1H NMR, 2D NMR and circular dichroism spectroscopic studies on the disulfide bond-constrained short peptides 4.7?4.9 with alternating α-aminoxy acids and α-amino acids suggest that a disulfide linker with three methylene units between adjacent α-amino acid residues could dramatically increase the stability of the 7/8 helix even in a mixed buffer/methanol solution. 1H NMR, 2D NMR and circular dichroism spectroscopic studies have also revealed that the hybrid soluble peptides C-free, N-free and Both-free containing α-amino acids and β-2,2-cyclopropyl-amino acids adopted a stable 8/8 helix in aqueous solution. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Chapter one reviews the recent progress in the synthesis of phosphonopeptides, pseudopeptides containing a phosphinic, phosphonic or phosphonamide linkage in place of an amide (peptide) linkage. It describes some of the general methods for the synthesis of these pseudopeptides; for example through couplings to the nitrogen of an α-aminophosphonic acid, or Michael addition to acrylates, as well as other methods, the scope for which are not as wide yet. It also provides a summary of the reported biological activities of this class of pseudopeptides. Chapter two contains the results and discussion for a novel method for the synthesis of α-hydroxy phenylphosphinate oligomers as well as hybrid oligomers containing α-hydroxy phenylphosphinic acid and α-amino carboxylic acids. In particular, synthesis of a series of dimeric α-hydroxy phenylphosphinates are reported. The analysis of these dimers by a combination of NMR spectroscopy, X-ray crystallography and computational methods shows intramolecular hydrogen bonding in these molecules depends on the relative configuration of the carbon and phosphorus atoms. However, although the development of the synthetic methods was successful, the separation and isolation of the diastereomers was not always possible, which hindered a more comprehensive analysis of folding patterns in these molecules. Chapter three contains the experimental procedures, preparation and spectroscopic characterisation of all the chemical compounds. Crystal data and details of crystal structures are in the Appendix.

The effect of hydrogen bonding on the conformation of organic moleculesunifies two projects in this thesis. In one project, the stability of the intramolecularhydrogen bond in derivatives of 2-guanidinobenzimidazole was studied bydynamic 1H NMR spectrometry. The impact that this intramolecular hydrogenbond had on the bond order of the neutral guanidino group and on the dynamicconformation of these aromatic structures was related to the concept of hydrogenbond-assisted resonance. In another project, an oligomer possessing repetitiveconformation and capable of much inter- and intramolecular hydrogen bondingwas designed and synthesized. The sensitivity of this oligomer to changes inanion concentration, as well as its own propensity to self-aggregate weremeasured.Hydrogen bonds found in many biological oligomers are connected thougha system of conjugated bonds. Guanidinobenzimidazole is a conjugated systemof carbon and nitrogen, connected by an intramolecular hydrogen bond. Severalderivatives of guanidinobenzimidazole were synthesized, and the effect ofseveral simple alkyl for hydrogen substitutions were studied.Guanidinobenzimidazole was used as a model to study what effect theconjugation and the intramolecular hydrogen bond have on each other.The formation of redundant low energy hydrogen bonds is universal inbiological oligomers. In DNA and RNA multiple hydrogen bonds are formed witha typical energy contribution of only 1-2 kcal/mol. Individually, these interactionsdo not give the biological oligomers their conformational stability, but togetherthey are very stable. The urea and amide based oligomers designed in the workand discussed in the thesis should form multiple hydrogen bonds withthemselves and/or with anionic guests. Chiral oligoureas were designed topossess this characteristic of cooperative conformation that so many biologicaloligomers and polymers share.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2007. / Title from title screen (site viewed Dec. 4, 2007). PDF text: x, 362 p. : ill. ; 13 Mb. UMI publication number: AAT 3271933 . Includes bibliographical references. Also available in microfilm and microfiche formats.

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references. Also available via the World Wide Web.