Reproduction de : Thèse de doctorat : Sciences des matériaux : Lille 1 : 2005. / N° d'ordre (Lille 1) : 3705. Résumé en français et en anglais. Titre provenant de la page de titre du document numérisé. Bibliogr. p. 167-175.

Thesis (Ph. D.)--Institute of Paper Chemistry, 1980. / Includes bibliographical references (leaves 75-78).

Thesis (Ph. D.)--Institute of Paper Chemistry, 1967. / Bibliography: leaves 49-51.

No description available.

No / The synthesis of 1,1-thiodisaccharide trehalose analogues in good to excellent yields by a Lewis acid (BF(3).Et(2)O)-catalysed coupling of sugar per-O-acetate with thiosugar is described. The reactivity of different sugar per-O-acetates and thiosugars is explored.

by Lee Chi-Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 74-78). / Abstracts in English and Chinese. / Acknowledgment --- p.ii / Table of Contents --- p.iii / Abstract --- p.v / Abstract (Chinese Version) --- p.vi / Abbreviation --- p.vii / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- General Background --- p.1 / Chapter 1.1.1 --- Valienamine --- p.2 / Chapter 1.1.2 --- Valienamine Derivatives --- p.4 / Chapter 1.2 --- Mechanistic Aspects of Glycosidase Inhibition --- p.6 / Chapter 1.2.1 --- General Background --- p.6 / Chapter 1.2.2 --- Mechanism of Enzyme Catalyzed Hydrolysis of Glycosides --- p.6 / Chapter 1.2.3 --- Types of Glucosidase Inhibitors --- p.7 / Chapter 1.2.4 --- Inhibition of Glycosidases by Valienamine Derivatives --- p.8 / Chapter 1.3 --- Previous Synthesis of Valienamine --- p.9 / Chapter 1.3.1 --- Enantiospecific Synthesis of Valienamine by Vasella and co-workers --- p.9 / Chapter 1.3.2 --- Enantiospecific Synthesis of Valienamine by Tatsuta and co-workers --- p.10 / Chapter 1.3.3 --- Synthesis of N-Alkyl Derivatives of Valienamine --- p.12 / Chapter 1.4 --- Previous Syntheses of Valienamine-containing Pseudodisaccharides and its Diastereomers --- p.12 / Chapter 1.4.1 --- Epoxide aminolysis --- p.12 / Chapter 1.4.2 --- Condensation of amine with ketone --- p.15 / Chapter 1.4.3 --- Synthesis of pseudoaminodisaccharide by Kapp and co-workers --- p.16 / Chapter 2. --- Results and Discussion --- p.18 / Chapter 2.1 --- General Strategy --- p.18 / Chapter 2.2 --- Syntheses of coupling precursors --- p.20 / Chapter 2.2.1 --- Syntheses of protected valienamine 65 and its 2-epimer80 --- p.20 / Chapter 2.2.1.1 --- Synthesis of Diol68 --- p.20 / Chapter 2.2.1.2 --- Synthesis of Diol67 --- p.21 / Chapter 2.2.1.3 --- Synthesis of protected valienamine 65 and its 2-epimer80 --- p.22 / Chapter 2.2.2 --- Syntheses of 6-deoxyaminosugars 63 and118 --- p.24 / Chapter 2.2.2.1 --- Synthesis of benzyl ether91 --- p.24 / Chapter 2.2.2.2 --- Synthesis of β-diol103 --- p.28 / Chapter 2.2.2.3 --- Synthesis of α-alcohol107 --- p.30 / Chapter 2.2.2.4 --- Synthesis of β-diol113 --- p.31 / Chapter 2.2.2.5 --- Syntheses of amines 63 and118 --- p.33 / Chapter 2.2.3 --- Syntheses of allylic chlorides --- p.34 / Chapter 2.3 --- Syntheses of pseudoaminodissaccharides --- p.36 / Chapter 3. --- Conclusion --- p.42 / Chapter 4. --- Experimental --- p.44 / Chapter 5. --- References --- p.74 / Chapter 6. --- Appendix --- p.79 / List of spectra --- p.79

trans-Sialidase de Trypanosoma cruzi (TcTS) pertence à família de glicoproteínas de superfície do parasita e constitui um dos poucos exemplos naturais de glicosiltransferases superficiais encontradas em eucariotes. T. cruzi é incapaz de sintetizar ácido siálico e utiliza esta enzima para retirar este monossacarídeo de glicoconjugados do hospedeiro para sialilar moléculas aceptoras, como mucina-GPI (glicosilfosfatidilinositol), presentes na sua membrana plasmática. Esta enzima é específica em catalisar, preferencialmente, a transferência de ácido siálico para moléculas de mucina, originando ligações -2,3 com moléculas de galactose aceptoras na superfície do parasita. Considerando a heterogeneidade das moléculas de mucina de T. cruzi, é necessário que novas moléculas sejam sintetizadas a fim de que estas atuem como substratos glicopeptídicos, os quais podem levar ao melhor entendimento das interações entre enzima e substratos e permitir o planejamento racional de inibidores seletivos. Por isso, o trabalho foi divido em três rotas sintéticas: (i) preparação do doador de galactose, (ii) preparação dos aceptores-doadores e (iii) acoplamento dos dissacarídeos com aminoácidos aceptores para obtenção dos blocos de construção. Apesar dos objetivos propostos inicialmente não terem sido totalmente alcançados, o trabalho desenvolvido durante esse período permitiu a síntese do doador de galactose (3) em três etapas, aceptor de galactose (6) em cinco etapas, dissacarídeo (11) na glicosilação de 6 com 3, aminoácidos aceptores (13 e 14) e também dos blocos de construção (17 e 18) decorrente do acoplamento de 11 com os aminoácidos aceptores. Não obstante, é importante ressaltar que apesar da extensa rota planejada, porém necessária, a síntese dos blocos de construção é inédita. Portanto, pode-se concluir que o trabalho trouxe relevante contribuição no que diz respeito à química de carboidratos e à disponibilização de dados espectrométricos de compostos orgânicos para a literatura. / Trypanosoma cruzi trans-sialidase (TcTS) belongs to the family of glycoproteins expressed on the surface of the parasite and constitutes one of the few examples of natural surface glycosyltransferases found in eucariotes. T. cruzi can not synthesize sialic acid itself and uses this enzyme to scavenge this monosaccharide from host glycoconjugates to sialylate acceptors molecules, such as GPI (glycosylphosphatidylinositol) mucins, that are present in parasite plasma membrane. This enzyme is specific to catalyze, preferentially, the transference of sialic acid to mucin glycoproteins, generating -2,3-linkages with acceptor galactose molecules in the parasite surface. Considering the heterogeneity of T. cruzi mucin molecules, its necessary to synthesize new compounds that can act as glycopeptide substrates, leading to a better understanding concerning the enzyme and substrates and allow the rational design of some selective inhibitors. Thus, this work was developed in three synthetic routes: (i) the synthesis of galactose donor, (ii) synthesis of donor-acceptors and (iii) coupling between disaccharides and acceptors amino acids in order to obtain building blocks. Despite of some objectives initially proposed had not been accomplished, the developed work during this period allow the synthesis of the galactose donor (3) in three steps, donor-acceptor (6) in five steps, disaccharide (11), acceptors amino acids (13 and 14) and also the building blocks (17 and 18). However, its important highlight that the synthesis of the building blocks by this necessary, but extensive, synthetic route is unpublished. Therefore, it can be concluded that the present work brought rich contribution concerning the carbohydrate chemistry and the availability of spectrometric data of organic compounds to the literature.

Heparan sulfate proteoglycan (HSPG) or heparan sulfate (HS) degradation may contribute to endothelial cell (EC) dysfunction in diabetes. HSPGs, syndecan and perlecan, contain a protein core with mainly HS glycosaminoglycans (GAGs) attached. HSPGs modulate growth factors and function in membrane filtering. Heparanase induction is likely responsible for diabetic HS degradation. Heparin protects endothelium and insulin regulates glucose metabolism. Our objectives were to observe HSPG changes by studying EC GAG content and gene expression of syndecan, perlecan and heparanase under hyperglycemic conditions with insulin and/or heparin treatment.<p> GAGs, including HS, were determined by the carbazole assay and visualized by agarose gel electrophoresis in porcine aortic EC cultures treated with high glucose (30 mM) and/or insulin (0.01 U/ml) for 24, 48 and 72 hours and/or heparin (0.5 µg/ml) for 72 hours. High glucose decreased cell GAGs and increased medium GAGs. GAGs increased with time in control cultures and in high glucose plus insulin treated medium. GAGs were decreased with insulin but increased with insulin or heparin plus high glucose.<p> Confluent cultured human aortic ECs were incubated with control medium, high glucose and/or insulin and/or heparin for 24 hours. Real time PCR determination showed that: high glucose increased heparanase, decreased syndecan and had no effect on perlecan mRNA; insulin or heparin with/without high glucose decreased and insulin and heparin with high glucose increased heparanase mRNA; heparin and insulin with high glucose increased but insulin decreased syndecan mRNA. Actinomycin D (10 µg/ml) inhibited heparanase and syndecan mRNA with high glucose plus insulin plus heparin and inhibited heparanase mRNA with high glucose compared to time 0 but not â-actin after addition for 0, 2, 4, 8 and 24 hours. Bioinformatic studies revealed that transcription factor Sp1 activates heparanase promoter by high glucose and may play a role in regulation of perlecan and syndecan promoters.<p> Insulin or heparin inhibited the reduction in EC GAGs and syndecan mRNA and induction in heparanase by high glucose, indicating their protective effect. Decreased GAGs by insulin may relate to the pathology of hyperinsulinemia. Transcriptional regulation by heparin and/or insulin may cause variation in gene expression of heparanase, syndecan and perlecan.

Heparan sulfate proteoglycan (HSPG) or heparan sulfate (HS) degradation may contribute to endothelial cell (EC) dysfunction in diabetes. HSPGs, syndecan and perlecan, contain a protein core with mainly HS glycosaminoglycans (GAGs) attached. HSPGs modulate growth factors and function in membrane filtering. Heparanase induction is likely responsible for diabetic HS degradation. Heparin protects endothelium and insulin regulates glucose metabolism. Our objectives were to observe HSPG changes by studying EC GAG content and gene expression of syndecan, perlecan and heparanase under hyperglycemic conditions with insulin and/or heparin treatment.<p> GAGs, including HS, were determined by the carbazole assay and visualized by agarose gel electrophoresis in porcine aortic EC cultures treated with high glucose (30 mM) and/or insulin (0.01 U/ml) for 24, 48 and 72 hours and/or heparin (0.5 µg/ml) for 72 hours. High glucose decreased cell GAGs and increased medium GAGs. GAGs increased with time in control cultures and in high glucose plus insulin treated medium. GAGs were decreased with insulin but increased with insulin or heparin plus high glucose.<p> Confluent cultured human aortic ECs were incubated with control medium, high glucose and/or insulin and/or heparin for 24 hours. Real time PCR determination showed that: high glucose increased heparanase, decreased syndecan and had no effect on perlecan mRNA; insulin or heparin with/without high glucose decreased and insulin and heparin with high glucose increased heparanase mRNA; heparin and insulin with high glucose increased but insulin decreased syndecan mRNA. Actinomycin D (10 µg/ml) inhibited heparanase and syndecan mRNA with high glucose plus insulin plus heparin and inhibited heparanase mRNA with high glucose compared to time 0 but not â-actin after addition for 0, 2, 4, 8 and 24 hours. Bioinformatic studies revealed that transcription factor Sp1 activates heparanase promoter by high glucose and may play a role in regulation of perlecan and syndecan promoters.<p> Insulin or heparin inhibited the reduction in EC GAGs and syndecan mRNA and induction in heparanase by high glucose, indicating their protective effect. Decreased GAGs by insulin may relate to the pathology of hyperinsulinemia. Transcriptional regulation by heparin and/or insulin may cause variation in gene expression of heparanase, syndecan and perlecan.

No description available.