Glycoproteins are proteins that are post-translationally modified with oligosaccharides. Due to the non-template-mediated biosynthesis of glycoproteins in the nature, glycoproteins always exist as heterogeneous mixtures with different glycan structures. In order to obtain the homogeneous glycoproteins with the well-defined glycan structures for an extensive investigation of the relationship between the structure and function of glycoproteins, synthetic strategies including chemical and chemoenzymatic synthesis have been employed and achieved great success over the past years. Among these approaches, our research group has developed a novel serine/threonine ligation (STL), which involved a chemoselective ligation between a peptide with a salicylaldehyde (SAL) ester at the C-terminus and an N-terminal serine or threonine of another peptide to generate the natural Xxx-Ser/Thr linkage (Xxx represents any amino acid) at the conjugation site. STL provides more possibilities for disconnection sites for convergent protein/glycoprotein synthesis. My research has been focused on the synthesis of MUC1 glycopeptides. MUC1 is a transmemberane glycoprotein expressed on the apical surface of most normal epithelial cells at low levels but highly overexpressed on the entire membrane of human epithelial tumor cells. In the extracellular part, MUC1 contains a variable number of tandem repeat (VNTR) units which consist of twenty amino acids with five potential O-glycosylation sites. As MUC1 has been shown asa promising target for the production of immunostimulating antigens, a variety of chemical assembly strategies have been applied for the development of MUC1 glycopeptide-based anticancer vaccines with high immunogenicity and tumor selectivity, including the construction of multivalent dendrimers presenting tumor-associated MUC1 glycopeptide antigens and the incorporation of various immunoadjuvants. In my studies, I have successfully synthesized the large MUC1 VNTR glycopeptides (40-mer and 80-mer sections) possessing tumor-associated Tn antigens via one and three consecutive STL reactions. On the other hand, the cyclic MUC1 glycopeptide-BSA conjugates has been successfully constructed. We are yet to test the immunological properties of synthetic MUC1 glycopeptide oligomers and MUC1-based glycoconjugates as anticancer vaccine candidates. In addition, inspired by STL, I have developed an aspartic acid ligation, in which a C-terminal peptide-SAL ester chemoselectively reacts with an N-terminal diol group of another peptide under the same conditions as STL to form a six-membered N,O-benzylidene acetal linked intermediate. Followed by treatment with acidsand selectiveoxidation, the natural Xxx-Asplinkage(Xxx represents any amino acid) is chemoselectively generated at the conjugation site. This STL-based aspartic acid ligation has been applied in the synthesis of a series of cyclic and linear peptides. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

by Man Kin Tse. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references. / 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.

by Chi-wai Wan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 129-136). / 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.

本論文敘述了 III-B類輪烷樹狀物的人工合成及其表徵。透過重覆(1) 經改良的 銅(I) 催化炔烴 -疊氮偶極環加成反應 (2) 生成醯胺鍵以及最後 (3) 格拉澤 -希偶聯反應合成第一代 (G1) 及第二初代 (G2 ’)IIIB類輪烷樹狀物。 銨鹽啞及冠醚被採用來組合成分支結構的偽輪烷。 III B類輪烷樹狀物被核磁共振波譜法及電噴霧離子化法－質譜所表徵。這項研究為 III-B類輪烷樹狀物合成研究提供不可或缺的雛型 。這項研究為超分子及高化學家開拓新的領域，給予他們研究III-B類輪烷樹狀物的特性及其生醫學和電子應用機會。 / In this thesis, the syntheses and characterizations of a series of Type III-B Rotaxane Dendrimers are described. First generation (G1) and prototypical second generation (G2’) Type IIIB Rotaxane Dendrimer, which incorporate rotaxane features as the branching units, were synthesized by employing consecutive (1) modified Copper-Catalyzed Alkyne-Azide Cycloaddition (CuAAC), (2) amide formation through stopper molecule and pseudorotaxanes, and (3) GlaserHay’s acetylene homo-coupling reaction. Pseudorotaxanes with ammonium thread and crown ether macrocycle were employed. The Type III-B Rotaxane Dendrimers were characterized by nuclear magnetic resonance (NMR) spectroscopy, electrospray ionisationmass spectrometry (ESI-MS). This study provides an indispensable prototype to the synthesis of novel Type III-B Rotaxane Dendrimer. It opened up great opportunity for supramolecular and polymer chemists to further explore the properties and biomedical and electronic application of the novel dendrimers. / Detailed summary in vernacular field only. / Ho, Kwok Wai. / "October 2012." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 49-51). / Abstracts also in Chinese. / Contents --- p.i / Acknowledgments --- p.ii / Abstract --- p.iii / Abbreviations and Acronyms --- p.v / Synthetic Studies Towards Type III-B Rotaxane Dendrimer / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Classification of Rotaxane Dendrimers --- p.2 / Chapter 1.2 --- Type II-B Rotaxane Dendrimer --- p.5 / Chapter 1.3 --- Application of Copper Catalyzed Alkyne Azide Cycloaddtion(CuAAC) in Rotaxane Synthesis --- p.8 / Chapter 1.4 --- Potential Application of Type III-B Rotaxane Dendrimer --- p.12 / Chapter 1.5 --- Aim of Project --- p.14 / Chapter Chapter 2 --- Synthetic Studies Towards of Type III-B Rotaxane Dendrimer / Chapter 2.1 --- Design and Synthesis of Type III-B Rotaxane Dendrimer --- p.15 / Chapter 2.2 --- Characterization of G1 and G2’ Type III-B Rotaxane Dendron/Dendrimer --- p.27 / Chapter 2.2.1 --- ¹H NMR Spectroscopy --- p.27 / Chapter 2.2.2 --- ¹³C NMR Spectroscopy --- p.32 / Chapter 2.2.3 --- Mass Spectrometry --- p.32 / Chapter 2.3 --- Conclusion --- p.38 / Chapter Chapter 3 --- Experimental Procedures / Chapter 3.1 --- General Information --- p.39 / Chapter 3.2 --- Experimental Procedures --- p.40 / References / Appendix / List of Spectra --- p.A1

Two approaches to the tricyclic core of the furanoeremophilane sesquiterpenoids are described. The first approach entails a projected Diels-Alder/retro Diels-Alder reaction of an acetylenic oxazole 64. Construction of the pivotal aldehyde 67 commenced from ketone 68. The acetyenic moiety was then introduced via a Felkin-Ahn addition of lithiopropyne to aldehyde 67. The final conversion of the cyclohexanone 83 to the acetylenic triflate 65 was unsuccessful. Attempts at addition of lithiated 2-methyloxazole 88 to ketone 83 were also unsuccessful. The second approach exploited a new annulation strategy. The aldehyde 64 was advanced to the 2, 4, 6-triisopropylbenzene sulfonylhydrazone 102 and a Shapiro reaction of 102 then provided alcohol 96. The furyl stananne 114 was readily prepared via a six-step sequence from acetylacetaldehyde dimethyl acetal 106. Unification of allylic bromide 90 and stannane 114 was accomplished through a Stille cross coupling methodology and the resulting product 113 was advanced to the aldehyde 116. However, attempts at further oxidation of this aldehyde to the required acid 89 failed. An alternative furyl stananne 124 with a tert-butyldimethylsilyl substituent at the C2 position was prepared from 3-furoic acid. An analogous sequence to that used with 113 led to aldehyde 131 which was successfully cyclized with the aid of trimethylsilyl trifluromethanesulfonate and 2, 6-lutidine to the tricyclic structure 132. Oxidation of the epimeric mixture of alcohols, followed by stereoselective reduction and removal of the tert-butyldimethylsilyl group from alcohol 134, gave (±)-6β-hydroxyeuroposin (4). Oxidation experiments with 134 were shown to convert the furan in this structure to a butenolide characteristic of the eremophilenolides. / Graduation date: 2004

Graduation date: 2001

Herein is described our work towards the total synthesis of the marine natural product (±)-chartelline C and the potent antibiotic (-)-platensimycin. Part 1 relates the (±)-chartelline C project. The first chapter reviews (±)-chartelline C’s isolation, biogeneity, and previously reported studies relevant to the area. Chapter 2 tells of our contributions including the development of a convergent, regioselective assembly of an indole-imidazole compound en route to the natural product. Chapter 3 includes the experimental details of this work and the characterization of previously unreported compounds. Part 2 recounts the (-)-platensimycin research project. Chapter 4 discusses the importance of the natural product and the relevant previous research reported. Chapter 5 describes our efforts in this area, culminating in the stereoselective synthesis of an intermediate closely related to a known compound, which was converted to the natural product. Chapter 6 includes the experimental details of this work and the characterization of previously unreported compounds. / text

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1990. / Includes bibliographical references. / Microfiche. / xi, 98 leaves, bound ill. 29 cm

No description available.

The in vitro translation products directed by cucumber necrosis virus (CNV) RNA were analyzed in both rabbit reticulocyte lysate and wheat germ extract cell-free translation systems. In rabbit reticulocyte lysates, one major protein of ca. 33 Mr was produced. In wheat germ extracts, four proteins of ca. 41, 33, 21 and 20 Mr were produced. Hybrid-arrested translation (HART) studies using synthetic CNV antisense RNA corresponding to the entire CNV genome demonstrated that the four major proteins synthesized from CNV virion RNA in wheat germ extracts are virus-specific translation products. The genomic locations of the CNV in vitro translation products were determined using a number of experimental approaches including: (1) HART using antisense RNA corresponding to selected regions of the CNV genome; (2) in vitro translation of synthetic messenger-sense CNV transcripts; (3) immunoprecipitation of in vitro translation products with CNV polyclonal antisera and (4) in vitro translation of size-fractionated CNV virion RNA. Together, these experiments demonstrated that the ca. 33 Mr protein is derived from the 5' proximal coding region, the ca. 41 Mr protein is derived from an internal coding region, and that at least one but probably both of the ca. 20 and 21 Mr proteins are derived from the 3' terminal coding region(s) of the CNV genome. In addition, immunoprecipitation experiments provided further evidence that the ca. 41 Mr protein is the viral coat protein. The size, number, and genomic locations of the CNV in vitro translation products reported here are in agreement with those predicted from nucleotide sequence data (Rochon & Tremaine, 1989). The natural template for the expression of downstream cistrons in the CNV genome was investigated by in vitro translation of sucrose fractionated CNV virion RNA as well as in vitro translation of messenger-sense synthetic transcripts. These studies indicate that in vitro, both subgenomic and genomic-length CNV RNA molecules may act as templates for the synthesis of the ca. 41,21 and 20 Mr proteins as well as the ca. 33 Mr protein. / Land and Food Systems, Faculty of / Graduate