Synthesis of Sphingoglycolipids Using Water-soluble Primers

 Enzymatic glycoconjugate synthesis is of great significance because regio- and stereoselectivity in glycoside bond formation can be achieved without any protective group or organic solvent [1]. Use of the glycopolymer cluster effects [2] is an excellent method to accelerate practical chemoenzymatic glycoconjugate synthesis because of the enhanced affinity of glycosyl transferases with water-soluble polymers having multivalent glycosyl acceptor substrates [3]. Water-soluble polymers carrying elongated oligosaccharide products are easily isolated from the reaction mixture by simple gel filtration or dialysis due to high molecular weight. The specific linkers that can be cleaved by the use of appropriate conditions have enabled easy procedures for product separation. Figure 1 is an outline of the enzymatic synthesis of sphingoglycolipids based on high performance polymer supports.
Fig.1. Strategy of Efficient Sphingoglycolipid Synthesis

Fig. 2. Various Sphingoglycolipids Syntheses Using Ceramide Glycanase From Leech
Here, a lactosyl ceramide-mimic polymer support is designed from L-serine and lactose as key starting materials. This water-soluble primer has been proved to be an excellent substrate for rat liver 2,3-sialyltransferase and porcine liver 2,6-sialyltransferase. These results suggest that the lactose residues on this macromolecule become glycosyl acceptors of common glycosyltransferases found widely in the biosynthetic pathways of glycoproteins. Furthermore, it was also demonstrated that this type of polymer is also an excellent substrate of ceramide glycanase known as an enzyme that hydrolyzes a glycoside bond between oligosaccharide and ceramide. The sugar-transferring activity of this enzyme can be used for the conjugation of oligosaccharide products with ceramide or sphingosine. This concept was applied to the synthesis of ganglioside GM3 and its analogs [4,5](Figure 2). The synthetic strategy using water-soluble primers will become a convenient and versatile method for the construction of a variety of sphingoglycolipids and related enzymes.
Shin-Ichiro Nishimura (Graduate School of Sciences, Hokkaido University)
References (1) Wong, CH, Halcomb RL, Ichikawa, Y, Kajimoto, T : Enzymes in Organic Synthesis: Application to the Problems of Carbohydrate Recognition (Part 1). Angew. Chem. Int. Ed. Engl. 34, 412-432, 1995
(2) Nishimura, S-I, Lee, YC: Synthetic Glycopolymers: New Tools for Glycobiology, Structural Diversity and Functional Versatility of Polysaccharides. edited by Dumitryu, Marcel Dekker, Inc. 15, 523-537, 1998
(3) Yamada, K, Fujita, E, Nishimura, S-I : High Performance Polymer Supports for Enzyme-assisted Synthesis of Glycoconjugates. Carbohydr. Res. 305, 443-461, 1998
(4) Nishimura, S-I, Yamada, K : Transfer of Ganglioside GM3 Oligosaccharide from a Water-Soluble Polymer to Ceramide by Ceramide Glycanase. A Novel Approach for the Chemical-Enzymatic Synthesis of Glycosphingolipids. J. Am.Chem. Soc. 119, 10555-10556, 1997
(5) Yamada, K, Matsumoto, S, Nishimura, S-I : Efficient Synthesis of Non -natural Ganglioside (pseudo-GM3) and Fluorescent Labelled lysoGM3 on the Basis of Polymer-Assisted Enzymatic Strategy. Chem. Commun. 507-508, 1999
Jun. 15, 2000

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