Leukocyte function-associated antigen 1 LFA

Selected adhesion molecules represent yet another antibody target. Adhesion molecules, such as LFA-1 (leukocyte function-associated antigen-1) and ICAM-1 (intercellular adhesion molecule 1), play central roles in promoting migration of inflammatory cells to the sites of damage. Such activities underlie many of the symptoms of conditions such as rheumatoid arthritis. Inhibition of adhesion molecule function by administration of antibodies raised against them may, therefore, demonstrate therapeutic potential in some instances. 

Key PMN, polymorphonuclear leukocytes EC, endothelial cell lymphs, lymphocytes CD, cluster of differentiation iCAM, intercellular adhesion molecule LFA-1, lymphocyte function-associated antigen-1 PECAM-1, platelet endothelial cell adhesion cell molecule-1. 

Inamura, N., Mekori, Y.A., Bhattacharyya, S.P., Bianchine, P.J. and Metcalfe, D.D. (1998) Induction and enhancement of FcERI-dependent mast cell degranulation following coculture with activated T cells dependency on ICAM-1- and leukocyte function-associated antigen (LFA)-l-mediated heterotypic aggregation. Journal of Immunology 160, 4026-4033. 

The ability of NOE matching to identify the correct pose from a collection of decoy poses was demonstrated on three test cases involving lead-like compounds bound to small proteins. One of these test cases involves muscle fatty acid-binding protein (mFABP) and the other two involve the leukocyte function-associated antigen 11-domain (LFA-1). As these results have been presented in detail elsewhere,1151 here we only summarize the results obtained when the BMRB average chemical shifts (diamagnetic protein statistics) were used for chemical shift predictions. The compounds used for these test cases are shown in Scheme 5.1 (compound 3 contains a proprietary core, which is represented by an ellipse). 

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