P-selectin blocking potency of multimeric tyrosine sulfates in vitro and in vivo

Bioorg Med Chem Lett. 2003 May 19;13(10):1709-12. doi: 10.1016/s0960-894x(03)00234-8.

Abstract

P-selectin blocking potency was investigated using synthetic monomeric and polymeric anionic compounds containing sulfate groups such as O-sulfotyrosine (sTyr) and/or sulfated Lewis structures. A non-carbohydrate-containing polyacrylamide conjugate sTyr-PAA (80% mol of sTyr) was a remarkably potent inhibitor of P-selectin binding in vitro, having an IC(50) value of 6 ng/mL (equivalent to 10 nM calculated on the basis of sTyr residues or 0.1 nM calculated by the mass of the macromolecule). The inhibitory effect of sTyr-PAA (80%) towards P-selectin is significantly greater than that of fucoidan (IC(50), 100 ng/mL). However, sTyr-PAA (80%) was less effective than fucoidan at reducing neutrophil extravasation in an in vivo rat model of peritonitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry
  • Animals
  • Chemotaxis, Leukocyte / drug effects
  • Dimerization
  • Disease Models, Animal
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Lewis X Antigen / chemistry
  • Lewis X Antigen / pharmacology
  • Neutrophils / drug effects
  • P-Selectin / drug effects*
  • P-Selectin / metabolism
  • Peritonitis / drug therapy
  • Protein Binding / drug effects
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry
  • Tyrosine / pharmacology*

Substances

  • Acrylic Resins
  • Lewis X Antigen
  • P-Selectin
  • tyrosine O-sulfate
  • Tyrosine
  • polyacrylamide