Studies on selectin blocker. 1. Structure-activity relationships of sialyl Lewis X analogs

J Med Chem. 1996 Mar 15;39(6):1339-43. doi: 10.1021/jm9506478.

Abstract

As part of our studies of selectin blockers, we prepared 1-deoxy-3'-O-sulfo LeX analogs (1-3), 1-deoxy-3'-O-phosphono LeX analogs (4), and 1-deoxy sLeX analogs (5-7), and examined their inhibitory activities against natural ligand (sLeX) binding to E-selectin, P-selectin, and L-selectin. The 1-deoxy sLeX 5 was up to 20 times more potent an inhibitor than the sLeX tetrasaccharide toward P- and L-selectin binding. This indicates that the modification of the 1 or 2 position of sLeX is useful in the design of a more potent selectin blocker.

MeSH terms

  • E-Selectin / metabolism*
  • L-Selectin / metabolism*
  • Lewis X Antigen / pharmacology*
  • Molecular Conformation
  • P-Selectin / metabolism*
  • Structure-Activity Relationship

Substances

  • E-Selectin
  • Lewis X Antigen
  • P-Selectin
  • L-Selectin