Digitized by Kansas Correctional Industries

by Wai Ming Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 71-74). / ACKNOWLEDGEMENTS --- p.i / CONTENTS --- p.ii / ABSTRACT --- p.iv / Chapter I. --- INTRODUCTION --- p.1 / Chapter I-1. --- Liquid Crystal Mesophases --- p.1 / Chapter I-1-1. --- Mesophases --- p.1 / Chapter I-1 -2. --- Classification of liquid crystals according to molecular order --- p.1 / Chapter I-2. --- Ferroelectric Liquid Crystals --- p.6 / Chapter I-3. --- "The Relationship Among Spontaneous Polarization, Tilted Angle and Response Time" --- p.7 / Chapter I-4. --- Applications of Liquid Crystals --- p.8 / Chapter I-5. --- An Ideal Ferroelectric Liquid Crystal --- p.9 / Chapter I-6. --- Recent Development in Chiral Liquid Crystals --- p.10 / Chapter I-7. --- Aim of The Present Research: Chiral Liquid Crystals from Carbohydrates --- p.15 / Chapter II. --- RESULTS AND DISCUSSION --- p.17 / Chapter II-1. --- "Synthesis of 4',4""-Heptoxybiphenyl (methyl 2-O-n- butyl-3,4-dideoxy-a-D-glucopyranosid) uronate (12) and 4',4""-Cyanobiphenyl (methyl 2-O-n-butyl -3,4-dideoxy-a-D-glucopyranosid) uronate (13)" --- p.17 / Chapter II-2. --- "Synthesis of 4',4''-Heptoxybiphenyl (methyl 2-O-n- butyl-3,4-di-O-methyl-a-D-glucopyranosid) uronate (14) and 4' ,4""-Cyanobiphenyl (methyl 2-O-n-butyl -3,4-di-O-methyl-α-D-glucopyranosid) uronate (15)" --- p.33 / Chapter II-3. --- Mesomorphic Phases and Transition Temperatures of Chiral Liquid Crystalline Compounds 12 and 13 --- p.42 / Chapter III. --- CONCLUSION --- p.47 / Chapter IV. --- EXPERIMENTAL SECTION --- p.48 / Chapter V. --- REFERENCES --- p.71 / List of Spectra --- p.75 / Spectra --- p.76

Cheng Cho-chak. / Thesis (M. Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 29-33; 63-65.

Sui-lam Wong. / Thesis (M.Phil.) -- Chinese University of Hong Kong. / Includes bibliographies.

Typescript, etc. / Digitized by Kansas Correctional Industries

Les glycosaminoglycanes (GAGs), des polysaccharides bio-actifs exprimés à la surface des cellules et dans la matrice extracellulaire, sont à l’origine d’un grand nombre de processus physiologiques et pathologiques tels le développement embryonnaire, la croissance cellulaire, l’homéostasie, etc. Parmi les biopolymères, ils offrent le plus grand potentiel d’information grâce à la variété de combinaisons et de modifications régio-sélectives des monosaccharides les constituant. Leur analyse structurale représente ainsi l’un des défis des glycosciences les plus difficiles à relever. De nouvelles approches basées sur la détection à l’échelle de la molécule unique permettent l’observation directe et la nano-manipulation de biomolécules. Principalement utilisées pour les acides nucléiques ou les protéines, ces approches ont rarement été appliquées à l’étude des polysaccharides. Nous présentons ici la détection à l'échelle de la molécule unique d’oligo-glycosaminoglycanes individuels confinés dans un nanopore protéique d’aérolysine et d’α-hémolysine. Nos résultats montrent la capacité de cette technique à discriminer les oligosaccharides d’acide hyaluronique selon leur degré de polymérisation, d’après la durée et la fréquence des blocages de courants. La preuve de la translocation a été montrée par spectrométrie de masse. Cette approche nous a permis de suivre la dépolymérisation enzymatique de l’acide hyaluronique et de déterminer ses paramètres cinétiques. D’autres oligosaccharides (l'héparine, le dermatane sulfate et le dextrane sulfate) ont été étudiés, présentant des signatures caractéristiques différentes, mettant en évidence des différences de structures et/ou conformations. / Glycosaminoglycans (GAGs) are bio-active polysaccharide expressed at the cell surface and in the extra-cellular matrix, which mediate cell-cell and cell-matrix interactions at the origin of a variety of physiological and pathological activities such as in embryonic development, cell growth, homeostasis, etc. Among all biopolymers, they offer the largest potential of information owing the incomparable variety of combinations and region-selective modifications of their building monosaccharides. The structural analysis of such complex carbohydrates is recognized as one of the most challenging task of glycosciences. New approaches based on single-molecule detection are currently arousing great interest in biology as it allows the direct observation and nano-manipulation of bio-molecules. Mainly applied to nucleic acids and proteins, these approaches have been not often used for the study of carbohydrates. We report here the detection of individual glycosaminoglycan oligosaccharides confined in aerolysin and α-hemolysin proteic nanopores. Our results show the capability of this new approach to discriminate hyaluronic acid (HA) oligosaccharides according to their polymerization degree based on the analysis of duration and frequency of the current blockades. This feature prompted us to apply this approach to the enzyme monitoring of the hyaluronidase-catalyzed depolymerization of HA and the determination of its kinetic parameters. Translocation has also been proved by mass spectrometry. Other oligosaccharides like heparin, dermatan sulfate and dextran sulfate, have also been studied, showing different characteristic “fingerprints”, due to structure and/or conformation differences.

Thesis (Ph. D.)--University of California, San Diego, 1982. / Vita. Includes bibliographical references (leaves 94-98).

Thesis (Ph. D.)--Oregon State University, 1984. / Typescript (photocopy). Includes bibliographical references (leaves 108-115). Also available on the World Wide Web.

Sulfated carbohydrates play key roles in a wide range of biological processes such as blood clotting, viral entry into cells, amyloidogenesis, neurite outgrowth, tumor growth and metastasis. However, their synthesis still remains a considerable challenge. A general approach to the synthesis of sulfated carbohydrates was examined in which sulfate group is incorporated at the beginning of the syntheses as a protected sulfodiester. Towards this end, a series of sulfuryl imidazolium salts (SIS), a new class of sulfating agents, was prepared and examined as reagents for incorporating 2,2,2-trichloroethyl-protected sulfate esters into monosaccharides. The SIS that contained a 1,2-dimethylimidazolium moiety proved to be a superior sulfating agent compared to SIS bearing no alkyl groups or bulkier alkyl groups on the imidazolium ring. Difficult O- and N- sulfations that required prolonged reaction times and a large excess of the SIS bearing a 1-methylimidazolium group were achieved in high yield and in less time when employing less than half the 1,2-dimethylimidazolium derivative. Efforts were then made to apply the sulfate protecting group strategy to the total synthesis of a class of chondroitin sulfate glycosaminoglycans. These studies revealed some of the limitations of the sulfate protecting group approach to the synthesis of sulfated oligosaccharides. Studies on the selective introduction and isomerization of the carbobenzyloxy protecting group into 2,3-diols of 4,6-O-benzylidene galactose derivatives are also reported.

Sulfated polysaccharides are widespread in nature. These compounds are implicated in a wide variety of important biological processes such as blood clotting, cell adhesion, and cell–cell communication. However, detailed characterization of their specific biological roles has proved to be very challenging. One reason for this is that the synthesis of even relatively small sulfated oligosaccharides still remains a considerable challenge. A general approach to the synthesis of sulfated carbohydrates was examined in which the sulfate group is incorporated at the beginning of the syntheses as a protected sulfodiester. Towards this end, a series of modified sulfuryl imidazolium salts were prepared and examined as reagents for incorporating 2,2,2-trichloroethyl-protected sulfate esters into monosaccharides.. A more efficient sulfating agent was obtained by incorporating a methyl group at the 2-position of the imidazolium ring. O-Sulfations that required prolonged reaction times and a large excess of the original sulfuryl imidazolium salt (SIS) which bears no alkyl groups on the imidazolium ring, were more readily achieved using the new reagent. Direct regioselective incorporation of TCE-protected sulfates into monosaccharides was achieved using the new imidazolium salt. We have also shown that the new SIS can also be used for the direct disulfation of monosaccharides and that trisulfated monosaccharides can also be prepared from the disulfated compounds. SIS’s bearing the TFE and phenyl groups, were readily prepared. In most instances, both TFE- and phenyl protected sulfated carbohydrates were easily prepared in good yields using SIS’s. Deprotection of the TFE group from secondary sulfates in carbohydrates and aryl sulfates was achieved in excellent yields using NaN3 in DMF. We applied the sulfate protecting group strategy towards the total synthesis of the tetrasaccharide portion of a disulfated glycosphingolipid called SB1a. Efficient routes were developed for the construction of the left- and right-hand protected disaccharide portions of the SB1a tetrasaccharide.