Abstract

In our effort to design a safe anti-cancer vaccine based on the tumor associated carbohydrate antigen Le^aLe^x, we are studying the cross-reactivity between the Le^a natural trisaccharide antigen and analogues in which the l-fucose, d-galactose, and/or d-glucosamine residues are replaced by l-rhamnose or d-glucose, respectively. We describe here the chemical synthesis of two such Le^a trisaccharide analogues. In one trisaccharide, d-glucose replaces d-galactose and in the second analogue l-rhamnose and d-glucose replace l-fucose and d-galactose, respectively. Introduction of the rhamnose and fucose moiety onto the poorly reactive 4-OH group of the N-acetylglucosamine residue in a disaccharide acceptor was successful after bis-N-acetylation of the amine group. These analogues will be used in competitive binding experiments with anti-Le^a antibodies and their solution conformations will be studied.

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Keywords: Synthetic carbohydrate-based anti-cancer vaccines; Cross-reactivity; Auto-immune reactions; Le^aLe^x analogues; Le^a analogues; GlcNAc-containing acceptors

Article Outline

1. Experimental

1.1. General methods

1.2. Methyl 2-acetamido-3-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-β-d-glucopyranoside (6)

1.3. Methyl 2-(N-acetylacetamido)-3-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-6-O-benzyl-2-deoxy-β-d-glucopyranoside (7)

1.4. Methyl 2-(N-acetylacetamido)-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-6-O-benzyl-2-deoxy-β-d-glucopyranoside (8)

1.5. Methyl 2-(N-acetylacetamido)-3-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-2-deoxy-β-d-glucopyranoside (11)

1.6. Methyl 2-(N-acetylacetamido)-3-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-4-O-(2,3,4-tri-O-acetyl-α-l-rhamnopyranosyl)-6-O-benzyl-2-deoxy-β-d-glucopyranoside (12)

1.7. Methyl 2-acetamido-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-2-deoxy-3-O-(β-d-glucopyranosyl)-β-d-glucopyranoside (13)

1.8. Methyl 2-acetamido-2-deoxy-β-d-glucopyranosyl-(1→3)-[α-l-fucopyranosyl-(1→4)]-β-d-glucopyranoside (2)

1.9. Methyl 2-acetamido-6-O-benzyl-2-deoxy-3-O-(β-d-galactopyranosyl)-4-O-(α-l-rhamnopyranosyl)-β-d-glucopyranoside (14)

1.10. Methyl 2-acetamido-β-d-glucopyranosyl-(1→3)-[α-l-rhamnopyranosyl-(1→4)]-2-deoxy-β-d-glucopyranoside (3)

Acknowledgements

Supplementary data

References