Combined chemical-enzymic synthesis of an internally monofucosylated hexasaccharide corresponding to the CD-65/VIM-2 epitope: use of a terminal α 2-6-linked N-acetylneuraminic acid as a temporary blocking group
✍ Scribed by Mohammed A. Kashem; Cong Jiang; Andre P. Venot; Gordon R. Alton
- Publisher
- Elsevier Science
- Year
- 1992
- Tongue
- English
- Weight
- 288 KB
- Volume
- 230
- Category
- Article
- ISSN
- 0008-6215
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✦ Synopsis
Sialylated and fucosylated lactosaminyl structures such as sialyl Lewis', sialyl dimeric Lewis", and its internally monofucosylated derivative have been proposed as ligands for the E-and the P-selectins'-4. The availability of pure synthetic materials is critical for the evaluation of the binding specificities. Glycosyltransferases have often been employed in chemo-enzymic syntheses in order to circumvent lengthy total chemical routes -.
' ' Particularly pertinent examples are the sialyl-Lewisa and sialyl-Lewis" oligosaccharides, which have been obtained by sequential enzymic sialylation and fucosylation'. Such syntheses follow the biosynthetic pathway "extension, sialylation, fucosylation"9,'0, which has also been proposed to lead to the terminal structure of the VIM-2 epitope, NeuSAc(aZ 3)Gal(~l-4)GlcNAc(~l-3~Gal(~1-4)[Fuc(~1-3)]GlcNAc, by selective internal fucosylation"~'*. Mutually exclusive glycosylation by the Gal(pl-4)GlcNAc cu2-6sialyltransferase and the GlcNAc al-3/4-fucosyltransferase occurs in the synthesis of asparaginyl linked oligosaccharides in glycoproteins13. The conformational preference of an cr-sialyl residue14 attached to the 6-hydroxyl of the terminal galactose may prevent the enzymatic fucosylation of the neighbouring N-acetylglucosamine.
In this communication, we report the synthesis of the hexasaccharide determinant of the VIM-2 epitope (5a,b) starting from tetrasaccharide la, by using