Thesis (doctoral)--Lund University, 1994.

Thesis (doctoral)--Lund University, 1994.

The synthesis of glycolipids containing a variable length polyethylene glycol spacer group between a glucuronic acid (glu) headgroup and a cholesterol (chol) tail glu-0CH₂(CH₂OCH₂ )nCH₂O-chol is described. The homologs (n=2,3,5) were prepared by reaction of an excess of commercially available tri, tetra and hexaethylene glycols with cholesteryl-p-toluene sulfonate. 3-O-(8-hydroxy-3,6-dioxaoctyl) cholest-5-ene (2), 3-O-(ll-hydroxy-3,6,9-trioxaundecyl)cholest-5-ene (3) and 3-O-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)cholest-5-ene (4) were produced, and yields were dependent on the amount of excess used. The headgroup was prepared by esterification and acetylation of glucuronolactone to produce methyl (1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyran)uronate which was then brominated at the anomeric carbon to produce methyl (2, 3, 4-tri-O-acetyl-α-D-glucopyranosyl bromide)uronate (1). The headgroup was coupled to the cholesteroxy oligoethylene glycols by a Koenig Knorr type reaction using freshly prepared silver carbonate as the catalyst. Methyl[3-O-(3,6-dioxaoctyl)cholest-5-en-3β-y1-2,3,4-tri-O-acetyl-β-D-glucopyranosid] uronate (5), Methyl[3-O-(3,6,9-trioxaundecyl) cholest-5-en-3β-yl-2,3,4-tri-0-acetyl-β-D-glucopyranosid] uronate (6), and Methyl[3-O-(3,6,9,12,15-pentaoxaheptadecyl)cholest-5-en-3β-yl-2, 3, 4-tri-O -acetyl-β-D-glucopyranosid] uronate (7) were produced with yields of up to 30%. The removal of the methyl ester and acetate protecting groups on the headgroup was accomplished using NaOH in a mixture of solvents followed by acidification with HCl to produce 3-O-(3,6-dioxaoctyl)cholest-5-en-3β-yl-β-D-glucopyranosiduronic acid (8) and 3-O-(3,6,9-trioxaundecyl)cholest-5-en-3β-yl-β-D-glucopyranosiduronic acid (9). Octaethylene glycol and dodecaethylene glycol were prepared using a solid supported synthesis. The solid polymer used was a trityl chloride functionalized polystyrene 1% divinyl benzene. Mono protected tetraethylene glycol was prepared and attached to the polymer. The protecting group was removed, and the hydroxy terminal was converted to a mesylate leaving group by reaction with methane sulfonyl chloride. To elongate the chain, the anion of tetraethylene glycol was prepared using sodium hydride in DMF. The tetraethylene glycol bound resin was added, and reaction continued at 120 °C for 24 hours. Cleavage of the resultant product from the polymer support yielded octaethylene glycol. Repetition of the mesylation and elongation steps followed by cleavage yielded dodecaethylene glycol. The oligoethylene glycols were purified by passage through a Fractogel 40S gel permeation column. Two different protecting groups for the tetraethylene glycol were tried. Trialkyl silyl groups were first attempted, but were abandoned due to reduced reactivity and monitoring difficulties during the deprotection. An acetate protecting group was finally used and deprotection was monitored with infrared spectroscopy. / Science, Faculty of / Chemistry, Department of / Graduate

Typescript (photocopy). / Digitized by Kansas Correctional Industries

In an attempt to evaluate the role of gangliosides as receptors for fibronectin, a series of Balb/c 3T3 variant cell lines, with a reduced ability to bind the ganglioside-specific ligand cholera toxin (CT), were examined. Initial characterisation showed that the cell lines displayed a generalised reduction in the synthesis of gangliosides more complex than GM3, but not of cell surface glycoproteins. There was no reduction in the levels of fibronectin found at the surface of the variants as compared with the parental cell line and all were able to spread and form focal contacts on fibronectin-coated substrates. These results suggest that complex glycolipids of the 'ganglio' series are not essential for Balb/c 3T3 cells to interact with fibronectin. The role of gangliosides as receptors for heat-labile toxin of E.coli (H-LT) was investigated using CT as a ganglioside-specific control. Both toxins bound to ganglioside GM1 and to Balb/c 3T3 cell membranes. Binding of 125I-labelled toxins was inhibited by either unlabelled toxin. There was no evidence to suggest that CT or H-LT recognised receptor(s), in Balb/c 3T3 cells, in addition to GM1. In rabbit intestinal brush borders at 0°C, there were more binding sites for H-LT than CT and 125I-H-LT binding could not be inhibited by unlabelled CT. At higher temperatures there was some inhibition of 125I-H-LT binding by CT. In Western blots H-LT recognised proteins co-migrating with the major brush border galacto-proteins. Toxin binding to brush borders from the Wistar strain of rat was similar. One of the 125I-H-LT binding sites may be the sucrase-isomaltase complex, since the toxin bound to brush border fractions enriched for enzyme activity. The data suggest that the major binding sites for H-LT in brush borders are not ganglioside in nature but may be glycoproteins.

No description available.

No description available.

No description available.

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)

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