Polyacetylene glycosides are natural products isolated from a variety of natural sources, primarily terrestrial plants and fungi. Polyacetylene glycosides isolated to date feature a linear and conjugated polyacetylene chain and a mono di-, or trisaccharide group in their structures. These compounds have been shown to possess a host of different biological activities, including anti-inflammatory effects, inhibition of nitric oxide production and histamine release, anti-bacterial activity, and the ability to inhibit the enzyme 12-lipoxygenase. The project described in this thesis focuses on polyacetylene glycosides and polyacetylene thioglycosides by glycosylating or thioglycosylating mono-, di-, or triyne alcohols, which have been synthesized using the Cadiot-Chodkiewicz reaction and Fritcsh-Buttenberg-Wiechell rearrangement. Twenty-seven polyacetylene glycosides and thioglycosides have been synthesized. Given the structural similarity of these compounds to bioactive natural products, we expected the molecules should have interesting biological activities. Thirty compounds have thus been assayed for cytotoxicity against MCF-7 breast lines, as well as anti-bacterial activity.

Human angiotensin-converting enzyme (ACE) is a key enzyme in the regulation of blood pressure via the renin-angiotensin and kallikrein-kinin systems. A number of orally active drugs have been developed over the years that target somatic ACE, for the treatment of hypertension, myocardial infarction and congestive heart failure. Protein structural information about ACE is an important key for the understanding of the mechanism and substrate-specificity of the enzyme. However, this information has only begun to be elucidated in the past year, with the solution of crystal structures of human testis ACE (tACE), and homologues Drosophila AnCE and human ACE2. tACE is identical to the C-terminal domain of somatic ACE, which consists of two homologous domains, each having a slightly different substrate-specificity. This thesis describes the purification, crystallisation and X-ray crystal structure-determination of a glycosylation-deficient mutant of tACE, tACEG1,3, to 2.9 &Aring / .

Thesis (M.S.)--University of Toledo, 2007. / Typescript. "Submitted as partial fulfillments of the requirements for the Master of Science Degree in Chemistry." "A thesis entitled"--at head of title. Bibliography: leaves 56-65.

Thesis (PhD) -- AUT University, 2007. / Includes bibliographical references. Also held in print (v, 215 leaves : ill. ; 30 cm.) in City Campus Theses Collection (T 573.154 NAR)

Thesis (Ph. D.)--University of Adelaide, Dept. of Plant Science, 1995? / Includes bibliographical references (p. 145-162).

Thesis (Ph. D.)--University of Adelaide, Dept. of Horticulture, Viticulture and Oenology, 1996? / Copies of author's previously published articles inserted. Includes bibliographical references (leaves 121-144).

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains x, 67 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 37-38).

Thesis (M.S. in chemistry)--Washington State University, August 2007. / Includes bibliographical references (p. 54-59).

Thesis (M.S.)--Montana State University--Bozeman, 2007. / Typescript. Chairperson, Graduate Committee: Hien Nguyen. Includes bibliographical references.

Magister Scientiae - MSc / Human angiotensin-converting enzyme (ACE) is a key enzyme in the regulation of blood pressure via the renin-angiotensin and kallikrein-kinin systems. A number of orally active drugs have been developed over the years that target somatic ACE, for the treatment of hypertension, myocardial infarction and congestive heart failure. Protein structural information about ACE is an important key for the understanding of the mechanism and substrate-specificity of the enzyme. However, this information has only begun to be elucidated in the past year, with the solution of crystal structures of human testis ACE (tACE), and homologues Drosophila AnCE and human ACE2. tACE is identical to the C-terminal domain of somatic ACE, which consists of two homologous domains, each having a slightly different substrate-specificity. This thesis describes the purification, crystallisation and X-ray crystal structure-determination of a glycosylation-deficient mutant of tACE, tACEG1,3, to 2.9 Å. The structure of tACE-G1,3 aligns closely with that of native tACE, indicating that the mutations did not alter the conformation. The ability to achieve minimal glycosylation of tACE for crystallisation purposes via mutation, rather than using expensive glycosidase inhibitors, iii should prove advantageous for further structural studies, such as the study of the binding of novel inhibitors. In all of the tACE structures thus far observed, the active site is closed off from the external medium in a deep cleft, so that it is unclear how a large substrate molecule could gain access. However, a hinge motion that opens this cleft has been observed in the structures of ACE2. Temperature factor and sequence comparison between tACE, tACE-G1,3, AnCE and ACE2 suggests the functional conservation of three flexible loop regions, as well as the sequence conservation of three constrained regions, involved in the hinge. Normal mode analysis reveals the intrinsic flexibility of tACE, and further suggests that a putative open form of tACE would behave similarly to the open form of ACE2. Based on these indications, a conservation of the ACE2 hinge-bending mechanism is proposed. Temperature factor analysis also reveals that subdomain II, containing bound chloride ions, is more structurally rigid than subdomain I, in all structures considered. Based on these results, lines of investigation are suggested that should yield insight into the mechanisms of action of ACE and its association with various substrates and inhibitors, ideally aiding in the development of novel drugs for the treatment of cardiac disease. / South Africa