Synthesis of 2-aminoethyl 3′-(N-glycolylneuraminyl)-β-actoside and neoglycoconjugates based thereon — a prototype of a cancer vaccine and artificial antigens for the control of immune response

Abstract

The 2 aminoethyl β glycoside of the trisaccharide 3´ (N glycolylneuraminyl)lactose was synthesized in the framework of studies of approaches to the preparation of synthetic tumor vaccines based on carbohydrate chains of tumor associated gangliosides and converted to the corresponding 2 (4 maleimidobutanoylamino)ethyl glycoside. The reaction of the latter with thiolated hemocyanin from the keyhole limpet Megathura crenulata (KLH) gave a carbo hydrate-protein conjugate, a tumor vaccine prototype containing about 250 trisaccharide ligands attached to a macromolecular KLH complex. A polyvalent conjugate with a polyacryl amide support was synthesized to be used as a coating antigen in the control of specificity and efficiency of immune response by enzyme linked immunosorbent assay (ELISA). * On the occasion of the 75th anniversary of the foundation of the N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences. 4.49 (d, 1 H, H(1) Gls, J 1,2 = 8.0 Hz); 4.48 (dd, 1 H, H(3) Gal , J 2,3 = 9.8 Hz, J 3,4 = 2.7 Hz); 4.42 (dd, 1 H, H(6a) Gls, J 6a,6b = 12.0 Hz, J 6b,5 = 1.7 Hz); 4.38 (dd, 1 H, H(9a) Neu , J 9a,8 = 2.6 Hz, J 9a,9b = 12.5 Hz); 4.14 (dd, 1 H, H(6b) Gls, J 6a,6b = 12.0 Hz, J 6b,5 = 4.9 Hz); 3.91-4.02 (m, 5 H, H(5) Neu , H(6a,6b) Gal , H(9b) Neu , OCH a H b CH 2 Cl); 3.84 (dd, 1 H, H(4) Glc ), Scheme 3

Carbohydrate chemistry in drug discovery

“…Carbohydrate-based anticancer vaccines have gained much scientific interest over the last few years. [112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] The glycosylation pattern and the density of cell-surface sugars are determined genetically. Cancer cells express aberrant surface carbohydrate structures, either in their sequence (truncated glycosylation), or in their increased expression.…”