Fluorinated glucosamine analogs useful for modulating post-translational glyscosylations on cells

Abstract

The present invention provides compositions and methods for inhibiting cell migration, e.g., lymphocytes and inflammation. The invention also provides an improved process for preparing fluorinated N-acetylglucosamines.

1 . A method of inhibiting migration of a leukocyte, comprising contacting a leukocyte with a fluorinated N-acetylglucosamine.  
     
     
         2 . The method of  claim 1 , wherein said N-acetylglucosamine is 2-acetamido-2-deoxy-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-D-glucopyranose or 2-acetamido-2-deoxy-1,4,6-tri-O-acetyl-3-deoxy-3-fluoro-D-glucopyranose.  
     
     
         3 . The method of  claim 1 , wherein said leukocyte is a lymphoid cell.  
     
     
         4 . The method of  claim 3 , wherein said lymphoid cell is a T-cell  
     
     
         5 . The method of  claim 4 , wherein said T cell is a Th 1 cell.  
     
     
         6 . The method of  claim 1 , wherein said leukocyte is a leukemic cell.  
     
     
         7 . The method of  claim 6 , wherein said leukocyte is a lymphoma.  
     
     
         8 . The method of  claim 7 , wherein said lymphoma is cutaneous lymphoma.  
     
     
         9 . The method of  claim 1 , wherein said N-acetylglucosamine is present at the concentration of 0.05 mM to 0.5 mM.  
     
     
         10 . A method of inhibiting cell proliferation, comprising contacting a cell with a fluorinated N-acetylglucosamine.  
     
     
         11 . The method of  claim 10 , wherein said cell is a hematopoietic cell.  
     
     
         12 . The method of  claim 11 , wherein said hematopoietic cell is a hematopoietic progenitor cell.  
     
     
         13 . The method of  claim 10 , wherein said cell is a leukocyte.  
     
     
         14 . The method of  claim 10 , wherein said leukocyte is a leukemic cell.  
     
     
         15 . The method of  claim 10 , wherein said cell is further contacted with a chemotherapeutic agent.  
     
     
         16 . The method of  claim 15 , wherein said chemotherapeutic agent is selected from the group consisting of daunorubicin (DNR), cytarabine (ara-C), idarubicin, thioguanine, etoposide, and mitoxantrone.  
     
     
         17 . A method of modulating differentiation of a cell, comprising contacting the cell with a fluorinated N-acetylglucosamine.  
     
     
         18 . The method of  claim 17 , wherein said cell is a hematopoietic cell.  
     
     
         19 . The method of  claim 18 , wherein said hematopoietic cell is a hematopoietic progenitor cell.  
     
     
         20 . A method of inhibiting migration of a hematopoietic cell, comprising contacting the hematopoietic cell with a fluorinated N-acetylglucosamine.  
     
     
         21 . The method of  claim 20 , wherein said hematopoietic cell is a hematopoietic progenitor cell.  
     
     
         22 . A method of decreasing an amount of HECA-452 epitope on a glycoprotein on a cell, comprising contacting the cell with a fluorinated N-acetylglucosamine.  
     
     
         23 . The method of  claim 22 , wherein said glycoprotein is PSGL-1 or CD44.  
     
     
         24 . The method of  claim 22 , wherein the amount of said glycoprotein on said cell in the presence of the fluorinated N-acetylglucosamine as compared to in the absence of the fluorinated N-acetylglucosamine differs by less than 10%.  
     
     
         25 . The method of  claim 22 , wherein the amount of said glycoprotein on said cell in the presence of the fluorinated N-acetylglucosamine as compared to in the absence of the fluorinated N-acetylglucosamine differs by less than 5%.  
     
     
         26 . The method of  claim 22 , wherein the amount of said glycoprotein on said cell in the presence of the fluorinated N-acetylglucosamine as compared to in the absence of the fluorinated N-acetylglucosamine differs by less than 1%.  
     
     
         27 . The method of  claim 22 , wherein said cell is a leukocyte, a tumor cell or a hematopoietic progenitor cell.  
     
     
         28 .- 45 . (canceled)