Identification of inhibitors for dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN)-carbohydrate interactions

CARB 80

M. Jack Borrok, jborrok@biochem.wisc.edu, Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706 and Laura L. Kiessling, kiessling@chem.wisc.edu, Departments of Chemistry and Biochemistry, University of Wisconsin, Madison, Madison, WI 53706.
Dendritic cell-specific intracellular adhesion molecule 3 [ICAM-3]-grabbing non-integrin (DC-SIGN) is a Ca2+-dependent lectin that binds mannose and fucose moieties of many glycoproteins. In the immune system, it functions in dendritic cell migration and antigen capture and presentation to T-lymphocytes. Many pathogens, most notably HIV-1 and Mycobacterium tuberculosis, have glycoproteins that also bind DC-SIGN. These pathogens can exploit the interaction with DC-SIGN, yet they evade the immune system via an unknown mechanism. It has been difficult to find effective ligands for C-type lectins, and many glycomimetics bind with relatively modest affinities. We have designed a high-throughput fluorescence-based competition assay for detecting small molecules that inhibit carbohydrate binding to DC-SIGN. Over 40,000 compounds have been screened and active compounds have been identified. Compounds that function as DC-SIGN inhibitors will be further characterized binding and in cell-based assays.
 

Chemical Glycobiology Symposium
7:00 PM-9:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Carbohydrate Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006