University of California

Genentech, Inc.

Syntex (u.s.a.) Inc.

Other

Steven D Rosen

Stefan Hemmerich

Mark S Singer

Yasuyuki Imai

Laurence A Lasky

Annette Bistrup

Ted A Yednock

Scott E Stachel

Carolyn Ruth Bertozzi

Jin Kyu Lee

Christopher M Sassetti

Kirsten Tangemann

Roman Nawroth

Joyce Geoffroy

Kun Huang

Novel sulfatases and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including various diagnostic and therapeutic agent screening applications. Also provided are methods of inhibiting tumor-induced angiogenesis and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of a subject sulfatase.

Sulfatases and methods of use thereof

Novel glycosylsulfotransferases (GST-4&#x3b1;, GST-4&#x3b2;, and GST-6) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including various diagnostic and therapeutic agent screening applications. Also provided are methods of inhibiting selectin mediated binding events and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of at least one of GST-4&#x3b1;, GST-4&#x3b2;, and GST-6.

Glycosyl sulfotransferases GST-4&#x3b1;, GST-4&#x3b2;, and GST-6

A novel human glycosylsulfotransferase expressed in high endothelial cells (GST-3) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting selectin mediated binding events and methods of treating disease conditions associated therewith.

Glycosyl sulfotransferase-3

Mammalian glycosylsulfotransferases expressed in high endothelial cells (HEC-GLCNAC6ST) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting selectin mediated binding events and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of at least one of HEC-GLCNAC6ST or KSGal6ST, or homologues thereof.

HEC-G1CNAC6ST

A novel human glycosylsulfotransferase expressed in high endothelial cells (GST-3) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting selectin mediated binding events and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of at least one of GST-3 or KSGal6ST, or homologues thereof

Methods of inhibition using glycosyl sulfotransferase-3

Podocalyxin like proteins (e.g. PCLP and PCLP-2) having selectin ligand activity are provided. Also provided are nucleic acid compositions encoding novel PCLP-2 proteins. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with podocalyxin like protein activity. In particular, methods of treating diseases associated with podocalyxin like protein selectin binding activity and/or chemokine presenting activity are provided, where such diseases include inflammation and the like.

Selectin ligands

Nucleic acid compositions encoding novel endoglycan proteins, as well as the novel endoglycan proteins, are provided. Also provided are methods of producing the subject nucleic acid and protein compositions. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including diagnostic and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with endoglycan activity. In particular, methods of treating diseases associated with endoglycan selectin binding activity and/or chemokine presenting activity are provided, where such diseases include inflammation and the like.

Endoglycan: a novel protein having selectin ligand and chemokine presentation activity

A novel human glycosylsulfotransferase expressed in high endothelial cells (GST-3) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting selectin mediated binding events and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of at least one of GST-3 or KSGal6ST, or homologues thereof.

Method of determining whether an agent modulates glycosyl sulfotransferase-3

Glycosly sulfortransferase-3

Sulfated disaccharides characterized by the ability to inhibit the binding of selectin to its physiologically-relevant ligand are disclosed. Included are efficient and inexpensive methods for producing the sulfated disaccharides, and methods for their therapeutic use and in in vivo and in vitro assays.

Sulfated disaccharide inhibitors of selectins, methods for synthesis and

The present invention provides novel assays for determining the ability of a test compound to inhibit intercellular adhesion mediated by a selectin receptor, such as the LHR. The assay involves coating a surface of a solid substrate with an antibody which specifically binds a selectin ligand. Preferred are antibodies against GlyCAM-1 which is a natural biological ligand for L-Selectin and also binds to P-Selectin and E-Selectin. A compound such as GlyCAM-1 is then bound to the antibodies. The test compound mixture putatively containing a selectin ligand is then brought into contact with a chimeric molecule. The test mixture might include any compound which might block or hinder binding between a selectin receptor and the ligand bound to the antibody. The chimeric molecule is comprised of an immunoglobulin bound to a selectin receptor and is introduced under conditions such that the selectin receptor portion of the chimeric molecule will bind to the selectin ligand bound to the antibodies on the surface if such binding is not blocked by the test compound. Bound chimeric molecules can be detected in a variety of ways such as by a conjugate compound of an anti-immunoglobulin antibody bound to enzyme such as alkaline phosphatase for the generation of color. Any test compounds which bind to the selectin receptor and block finding can be isolated, analyzed and identified.

Assays for inhibitors of leukocyte adhesion

Compositions are administered to a patient (preferably by injection and locally) to treat a variety of conditions including inflammation associated with trauma and with certain aspects of diseases such as rheumatoid arthritis, psoriasis, insulin-dependent diabetes, cutaneous lymphomas, duodenal ulcer, chronic proctitis, lymphocytic thyroiditis, hemorphagic shock, reperfusion injury during transplantation and multiple sclerosis. The compositions are pharmaceutically acceptable injectable formulations which include an active component in a pharmaceutically acceptable carrier. The active component is a chlorate or selenate which inhibits the natural biochemical sulfation process and/or a sulfatase enzyme which removes a sulfate from a specific position of a saccharide molecule which makes up a part of a natural ligand for L-selectin. Removal of the sulfate from the ligand hinders the ability of the ligand to bind to its natural receptor (i.e. L-selectin) and thereby hinders a biochemical chain of events which results in inflammation.

Treating inflammation via the administration of specific sulfatase

DNA isolates coding for the lymphocyte homing receptor and methods of obtaining such DNA are provided, together with expression systems for recombinant production of the lymphocyte homing receptor useful in therapeutic or diagnostic compositions.

Growing community of inventors

San Francisco, CA, United States of America

Steven D Rosen