Small Molecules as Structural and Functional Mimics of Sialyl Lewis X Tetrasaccharide in Selectin Inhibition: A Remarkable Enhancement of Inhibition by Additional Negative Charge and/or Hydrophobic Group

摘要

Several sialyl Lewis X (SLe~x) mimics that contain the essential functional groups for receptor interaction and a negative charge or a hydrophobic group have been developed as inhibitors of E-, P-, and L-selectins. Some of the mimics exhibit selectin nihibition activities 10~3-10~4 -fold more potent that does the natural ligand tetrasaccharide, with IC_50 in the low micromolar to high nanomolar range.