No description available.

by Tse Chung Ming. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1987. / Bibliography: leaves [148]-[173].

No description available.

Gamma-butyrolactones (GBLs) are signaling molecules produced by Streptomyces that play a key role in secondary metabolite production. Secondary metabolites, also known as natural products, have been used extensively in medicine and agriculture due to their bioactive properties. Genomic sequencing of the biosynthetic gene clusters (BGCs) from Streptomyces shows that only a small fraction of their secondary metabolites has been discovered. Activation of these silent BGCs has reinvigorated natural products chemistry as researchers become aware of the potential reservoir of novel lead compounds that remain unmined. One such GBL produced by Streptomyces is avenolide, responsible for activating production of avermectin, an anti-parasitic drug with over $850 million annual sales. In the work presented here, progress was made towards accessing the molecule avenolide in a synthesis commendable to derivatization with the aim of creating a library of avenolide-like molecules that could potentially “unlock” cryptic biosynthetic gene clusters and lead to the discovery of new bioactive secondary metabolites.

Hak-fun Chow. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1981. / Bibliography: leaves 70-73.

本文描述了碳環核苷的發展過程，同時也描述了將不同環融合在五元碳環上的方法來對碳環核苷的構象進行鎖定。 / 以D-核糖為起始原料，經過12 步反應並以分子內的Diels-Alder 反應 (IMDA)為關鍵步驟合成出了關鍵的中間體192，它的總產率為27%。通過對中間體192中的環己烯的結構進行修飾，經過3-4 步反應成功合成出了7 個具有雙環[4.3.0]壬烷結構的碳環核苷（185-191），它們的構型也通過其X 光單晶結構圖來進行確定。[附圖] / 以一價銅催化端炔和疊氮化物的Huisgen 環加成反應為關鍵步驟，成功地合成出了12 個具有雙環[4.3.0]壬烷結構的碳環三唑核苷。[附圖] / 同時，我們也合成12 個具有雙環[4.3.0]壬烷結構的碳環三唑核苷羧酸。[附圖] / 另外，我們也合成出了两個在三唑環上含有羧酸的碳環三唑核苷（298 和 299）。[附圖] / 最後，我們還合成出了16 個含有大基團叔丁基羧酸酯的碳環三唑核苷(260-263, 273-276, 286-289 和294-297)。[附圖] / In this thesis, a review regarding the development of carbobicyclic nucleosides and conformationally locked carbobicyclic nucleosides by fusing different rings onto the five-member ring was presented. / The key intermediate 192 was synthesized from D-ribose in 12 steps with 27% overall yield, using an Intramolecular Diels-Alder reaction (IMDA) as the key step. By modification of the cyclohexene ring, seven carbobicyclic adenosine analogues 185-191 with a bicyclo[4.3.0]nonane framework were prepared successfully from intermediate 192 in 3 to 4 steps and their conformations were examined by X-ray crystallography [with diagram]. / Twelve carbobicyclic ribavirin analogues 232-239 and 250-253 with a bicyclo[4.3.0]nonane framework were synthesized successfully by using a copper catalyzed azide-alkyne cycloaddition (Huigsen reaction) as the key step [with diagram]. / Another twelve ribavirin analogues bearing a carboxylate group (264-267, 277-280 and 290-293) with a bicyclo[4.3.0]nonane framework were also obtained [with diagram]. / Furthermore, two more ribavirin analogues bearing a carboxylic acid in triazole (298 and 299) with a bicyclo[4.3.0]nonane framework were obtained. [with diagram] / Finally, twelve ribavirin analogues bearing a tert-butyl carboxylate ester (260-263, 273-276, 286-289 and 290-293) with a bicyclo[4.3.0]nonane framework were also obtained [with diagram]. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Fanglin. / Thesis (Ph.D.) Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 175-187). / Abstracts also in Chinese.

Licenciatavhandling Uppsala : Sveriges lantbruksuniversitet, 2009. / Härtill 4 uppsatser.

Biopeptides are synthesised as large pro-protein precursors that have to undergo proteolytic cleavage at positively charged amino acids (Lys and Arg) in order to become active. This cleavage is mediated by a family of subtilin/kexin related calcium dependent serine endoproteinases named prohormone convertases. The present thesis focuses on the endocrine member of the family named PC1/3. PC1/3 is expressed in the regulated secretory pathway of endocrine and neuroendocrine cells, where it was shown to activate various peptide hormones such as proopiomelanocortin (POMC), pro-insulin and pro-glucagon. PC1/3 is synthesized as a large precursor containing a signal peptide, a propeptide, a catalytic domain, a P domain and a C-terminal domain. The activation of the enzyme requires the sequential removal of the signal peptide, the propeptide and ultimately the C-terminal domain. / The structural characterisation of the enzyme is compromised by the difficulty in producing a sufficient amount of recombinant PC1/3. In this thesis it is clearly demonstrated that the production of PC1/3 using Baculovirus technology can be greatly improved by modifying the expression vector in insect cells (Spodoptera frugiperda). In addition, the intracoelemic injection of insect larvae (Tricoplusia ni) with the Baculovirus encoding the recombinant PC1/3 is shown to be a very efficient method for the production of a large amount of prohormone convertases. / It was previously demonstrated that the propeptide is essential for the folding of the enzyme and act as a tight binding inhibitor of the enzyme until the latter reaches the appropriate compartment for substrate cleavage. To assess the role of certain residues within the propeptide in the inhibition of the cognate enzyme, a mutational analysis by alanine scan was conducted. The results demonstrate that the substitution of a single amino acid can affect markedly the inhibition behavior, potency and selectivity of the propeptide towards the enzyme. Moreover, this mutational analysis allowed the first experimental mapping of the sequence involved in propeptide degradation once its function is achieved. / However, PC1/3 also possesses a C-terminal domain which must also be cleaved to allow the full activation of the enzyme. Previous studies showed that this domain is implicated in the sorting of the enzyme to secretory granules. In addition, over expression experiments showed that the C-terminal domain can inhibit the cleavage of certain substrates by PC1/3. The results, presented here, suggest that the CT-peptide acts as a non-essential activator of PC1/3, in vitro, which adds a supplementary level of complexity to the activation process of the enzyme. / Finally, based upon our results, it can be proposed that PC1/3 is a very complex enzyme capable of controlling its enzymatic activity through the coordinate action of its various domains. This exceptional mode of self-regulation is unique among all protease families.

No description available.

The syntheses of the unsymmetrical 14-membered bismacrolides have been reviewed. A total synthesis of clonostachydiol, the latest to join this family, has been attempted using trimethylsilyl acetylene as the builiding block and palladium catalyzed reactions for the formation of key bonds. The alkyne groups were introduced by Stille coupling of trimethylstannylethynyltrimethylsilane with an acid chloride for one fragment and by addition of lithiotrimethylsilyl acetylene to an aldehyde for the other. Lactic acid derivatives were chosen as starting materials for both fragments, thus introducing two of the chiral centers. The remaining stereocenters were introduced using stereoselective reductions of ketones.