Unknown

The effect of A-286982 on ICAM-1-Ig and compound 2B binding to the receptor was clearly different. In the LFA-1/ICAM-1 ELISA, the ICAM-1-Ig curves were shifted rightward to higher EC50 values; however, the maximum binding of ICAM-1-Ig to LFA-1 decreased considerably with increasing concentrations of A-286982 (20 and 50 μM). The reduction in maximal binding and rightward shift of the ligand binding curves with increasing A-286982 concentration are reflective of allosteric inhibition. A-286982 causes reductions in both ligand affinity and binding capacity; this demonstrates that A-286982 is an insurmountable antagonist of ICAM-1-Ig binding. The A-286982 binding data serve as an illustrative control for allosteric effects on small molecule and protein ligand binding to LFA-1 in the binding experiments.