Lactosyl ceramide

Nishimura and Yamada [10-11] introduced a water-soluble polymeric support having a linker recognized by ceramide glycanase for a synthesis of ganghoside GM3 (17). Synthesis of the polymerizable lactose derivative (14) with a ceramide glycanase sensitive linker is shown in Scheme 10.3. The lactosyl ceramide (Lac-Ger) mimetic glycopolymer (15) is obtained from the monomeric precursor (14) by co-polymerization with acrylamide. 

The lactosyl ceramide analogue (39 c) was also obtained by condensation, in acetone-methanol, of 4-0-triflyl galactosyl sphingosine (34c) with thiogalactose (8 c) generated in situ from the corresponding pseudothiourea derivative [38]. 

Both protein- and lipid-bound carbohydrates are present in milk lipid globule membrane (Table 10.2). Lipid-bound carbohydrates, present predominantly in glucosyl and lactosyl ceramides and in gangliosides,... 

The galactose bears a 3-sulfate group in cerebroside sulfatides, e.g., in lactosyl ceramide sulfate ... 

Ogawa and co-workers [97] have synthesised the complete glycosphingolipid (361) containing the terminal tetrasaccharide (356) of the Leb antigen attached to lactosyl ceramide. The lactose derivative (95), prepared by the action of trimethylamine — borane and aluminium chloride [99] on the benzylidene derivative (94), was condensed with the thioglucoside (362) in the presence of methyl triflate and molecular sieve to give the trisaccharide (363). This was deacetylated and the product (364) condensed... 

In addition to the cerebrosides, which contain only one carbohydrate residue, there are other glycosphingolipids in mammalian cells that contain more than one sugar component. These oligosaccharide derivatives are called globosides. For example, lactosyl ceramide (1-O-lactosyl-A acylsphingosine) is a constituent of the erythrocyte membrane. Ceramide trihexoside accumulates in the kidneys of patients with Fabry s disease, due to the lack of a lysosomal a-galactosidase A activity. 

Lactosyl ceramide synthase is a pi-4 galactosyl transferase (40). Lactosyl ceramide is the only glycoconjugate that contains lactose (as opposed to lactosamine). Lactosyl ceramide is the substrate for several glycosyl transferases that then define a core sequence of glycosphingolipids. The Globo series is defined by an al-4 galactosyl transferase activity (41, 42) to make initially globotriaosyl ceramide [also defined as the p ... 

Jeckel D, Karrenbauer A, Burger KNJ, van Meer G, Wieland F. Glucosylceramide is synthesized at the c)bosolic surface of various Golgi subfractions. J. Cell Biol. 1992 117 59-267. Lannert H, Bunning C, Jeckel D, Wieland F. Lactosyl ceramide is synthesized in the lumen of the Golgi apparatus. FTiBS Lett. 1994 342 91-96. 

Lactosyl ceramide (GL2a) Galj31 4Glcj31 Cer Major glycolipid in most non-neural tissue... 

Inhibitor ST6GalC K values (mM) ST3GalF Lactosyl-ceramide a-2,3-sialyl-transferase Ref(s). 

Biochemical identification and quantification of glucosyl- and lactosyl-ceramide has widely benefited of LC tandem MS method. A general method using l- henyl-3-methyl-5- yrazolone derivatives (Ramsay et ah, 2005) of urinary oligosaeeharides prior to analysis by electrospray ionization-tandem MS has been adapted to enable assay of large number of samples. PMP derivatization method was initially deseribed by Honda (Honda et ah,... 

Schmidt s group15 reported the first synthesis of the lactosyl ceramides 44 (Scheme 6). Reaction of excess n-tetradecylmagnesium bromide with 35 in THF at 60°C afforded a 1 1 mixture of d-arabino- and L-xylo-octadecanetetrol derivatives, 36a and 36b, respectively. Reactions at lower temperature or in different solvent did not result in a dramatic change in the ratio of 36a and 36b. It is interesting, however, that the addition of salts, such as the copper bromide-dimethyl sulfide complex or titanium tetrachloride, as a catalyst led... 

---