Alberta Research Council Incorporated

Chembiomed, Ltd.

Andre P Venot

Mohammed A Kashem

Pandurang V Nikrad

Robert M Ratcliffe

Richard H Smith

S Zaheer Abbas

Wasimul Haque

Robert M Ippolito

H Rizk Hanna

Cong Jiang

Om P Srivastava

M Abdul Mazid

Frank M Unger

Paul Bird

The present invention is drawn to methods for the synthesis of sialyl Lewis.sup.x derivatives modified at the C-2 and/or C-6 position of GlcNAc employing chemoenzymatic synthesis. The derivatives find use in the treatment and prevention of diseases.

Modified sialyl Lewis.sup.x compounds

The present invention is drawn to methods for the synthesis of Lewis.sup.a derivatives modified at the C-2 and/or C-6 position of GlcNAc employing chemo-enzymatic synthesis. The derivatives find use in the treatment and prevention of diseases.

Modified sialyl Lewis.sup.a compounds

The present invention is drawn to methods for the synthesis of sialyl Lewis.sup.x derivatives modified at the C-2 and/or C-6 position of GlcNAc employing chemo-enzymatic synthesis. The derivatives find use in the treatment and prevention of diseases.

Disclosed are methods for reducing the degree of antigen induced inflammation in a sensitized mammals. The disclosed methods employ oligosaccharide glycosides related to blood group determinants having a type I or type II core structure wherein the administration of such oligosaccharide glycosides is after initiation of the mammal's immune response but at or prior one-half the period of time required to effect maximal antigen-induced inflammation.

Time dependent administration of oligosaccharide glycosides related to

The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

Sialic acid glycosides, antigens, immunoadsorbents, and methods for

Disclosed are novel Lewis.sup.x and Lewis.sup.a analogues, pharmaceutical compositions containing such analogues, methods for their preparation and methods for their use.

Immunosuppressive and tolerogenic modified Lewis.sup.x compounds

Monofucosylated and monosialyated derivatives of the compound .beta.Gal(1-4).beta.GlcNAc(1-3).beta.Gal(1-4).beta.GlcNAc-OR, where R is hydrogen, a saccharide, an oligosaccharide or an aglycon moiety have been found to be useful in modulating a cell-mediated immune inflammatory response in mammals.

Methods for the synthesis of monofucosylated oligosaccharides

Disclosed are methods for the preparation of monofucosylated and sialylated derivatives of the compound .beta.Gal(1-4).beta.GlcNAc(1-3).beta.Gal(1-4).beta.GlcNAc-OR. In particular, the methods of this invention provide for a multi-step synthesis wherein selective monofucosylation is accomplished on the 3-hydroxy group on only one of the GlcNAc units found in the .beta.Gal(1-4) .beta.GlcNAc (1-3) .beta.Gal (1-4) .beta.GlcNAc-OR compound. In this step, monofucosylation is achieved by use of the .alpha.(1-3)fucosyltransferase.

Disclosed are methods for the enzymatic synthesis of alpha-sialylated oligosaccharide glycosides. Specifically, in the disclosed methods, sialyltransferase is activated to transfer an analogue of sialic acid, employed as its CMP-nucleotide derivative, to an oligosaccharide glycoside. The analogue of sialic acid and the oligosaccharide employed in this method are selected to be compatible with the sialyltransferase employed.

Methods for the enzymatic synthesis of alpha-sialylated oligosaccharide

The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the a anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

The stereochemistry of sialylation of an acceptor saccharide to obtain an a (2-3) or a (2-6) linkage is controlled to favor the a anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate a (2-3) and a (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

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Edmonton, Canada

Andre P Venot