The three dimensional structure of both a ligand and its cognate receptor are required for the success of structure-assisted drug design. This thesis reports the crystal structure of hectochlorin, a small, bioactive molecule, and the steps toward determining the crystal structure of an RNA molecule that is an attractive target for drug design. The absolute structure of hectochlorin, a cytotoxic, secondary metabolite isolated from Lyngbya majuscula, is reported herein. Specifically, the absolute configuration of hectochlorin, as determined by x-ray crystallography, is reported as 6S, 7S, 10S, 31S. Marine natural products are interesting as a source of novel chemical compounds that are potentially valuable as therapeutic agents, or have industrial applications. The absolute structure provides a model that serves as a starting point for rational drug design synthesis. In a second study, results are reported from attempts to crystallize a biologically important RNA structure, the trans-acting response element, (TAR), for the determination of its structure by x-ray diffraction, and ultimately, providing an initial model for structure-assisted drug design targeted against HIV. Crystals, of biologically relevant TAR sequences, greater that 0.1 x 0.1 x 0.1 mm�� in size, both in the presence and absence of a cognate ligand analogue, have been obtained. These crystals have been shown to be of poor diffraction quality, but the initial crystallization conditions provide a starting point for optimization that may yield higher quality crystals. / Graduation date: 2001

No description available.

Chan Siu Hong. / "December 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 172-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Licentiatafhandling.

Recent concern over the potential environmental impact of highway construction and repair materials on surface and ground waters has lead to extensive laboratory screening and subsequent testing of a set of new materials and waste amended mixes. As part of Phase II of a three-phase project for the National Cooperative Highway Research Program, a fate and transport model for the assessment of this impact has been written. The model predicts concentrations and loads of contaminants as well as toxicities for the leachates in both surface and subsurface environments. The model addresses four specific "reference environments": an impermeable highway surface, a permeable highway surface, a vertical piling, and a filled borehole. Six materials are examined in detail: crumb rubber asphalt concrete. SEMASS asphalt concrete, foundry sand asphalt concrete, ammonical copper zinc arsenate treated wood, and methyl methacrylate deck sealer. A statistical approach to relating toxicity to the concentration of a chemical "surrogate" forms the basis for prediction of toxicity in the leachates. All fate and transport prediction methods are based on physical and mathematical descriptions of the near-highway environment. Surface runoff is calculated using kinematic wave theory coupled with leaching, photolysis and volatilization, flow through pavement cracks is based on continuity, and subsurface transport is based on a plug flow model with linear or Freundlich sorption and biodegradation. Explicit finite difference numerical methods are used for both surface leaching and subsurface transport. A search engine is provided for examination of all laboratory results. / Graduation date: 1999

Graduation date: 1991

2,5-diketopiperazines peculiar heterocyclic system found in several natural products constitutes a rich source of new biologically active compounds. The wide spectrum of their biological properties points to various therapeutic possibilities. Introduction of structural rigidity, resulting in diketopiperazine derivatives containing a pyridine ring that can form an intramolecular hydrogen bond,and shows an interesting activity. In our research, we hope to probe further the importance of structural rigidity with regards to biological activity. We hope to replace the hydrogen bonding between the pyridine ring and amide nitrogen with a covalent link. This will further restrict the rotation and isomerization of the Z-double bond.

Ph.D.

Ph.D.

Not available / text