Alberta Research Council Incorporated

Chembiomed, Ltd.

Mohammed A. Kashem

Abdul M. Mazid

Mohammed A Kashem

Andre P Venot

Pandurang V Nikrad

Richard H Smith

Wasimul Haque

M Abdul Mazid

Robert M Ippolito

H Rizk Hanna

Cong Jiang

Om P Srivastava

Frank M Unger

Paul Bird

Abdul M Mazid

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

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

Specific sialyl transferases (ST) are important enzymes in the manufacture of carbohydrate moieties useful for pharmacological purposes and for diagnostic and clinical procedures. The invention offers simplified methods to isolate highly specific forms of these ST enzymes by taking advantage of the affinity of the ST for its acceptor substrate in the presence of the sialyl-CMP analogs, such as CDP. Specifically exemplified are isolation of the alpha 2,3-ST, specific for Le.sup.c or LacNAc, and alpha 2,6-ST specific for LacNAc.

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Edmonton, Canada

Mohammed A Kashem