Voprosy meditsinskoi khimii (ISSN 0042-8809)

Inhibitory activity of monomeric and polymeric selectin ligands

   
Ushakova N.A., Preobrazhenskaya M.E., Nifant'ev N.E., Usov A.I., Pochechueva T.V., Galanina O.E., Bovin N.V.
PubMed Id: 10635531
Year: 1999 vol: 45  issue:5  pages: 375-383
Abstract: The ability of tetrasaccharides (SiaLex, SiaLea, HSO3Lex),their conjugates with polyacrylamide (40 kDa), and several other monomeric and polymericsubstances to block selectins has been compared with that of polysaccaride fucoidan. Twoassay systems were used: one was constructed on the base of recombinant E-, P-, andL-selectins; the other was a rat model of peritoneal inflammation. IC50 valuesfor the neoglycoconjugate SiaLea-PAA were 6, 40, and 85 m Mwith the recombinant E-, P-, and L-selectins, respectively; all monomeric inhibitors wereabout two orders of magnitude weaker. PAA-conjugates, containing as a ligandtyrosine-o-sulfate in addition to one of the above mentioned oligosaccharides, were themost potent synthetic blockers. Compared with the most potent of the known inhibitors,fucoidan, bi-ligand glycoconjugate HSO3Lea-PAA-sTyr, displayed in vitro similaractivity in blocking L-selectin, while its activity towards P-selectin was ten timeslower. All the synthetic polymers tested were able to inhibit neutrophil extravasation toinflammation site, acting in concentration about 10 mg/kg. Thus, the effect of SiaLex isconsiderably more effective in vivo than in vitro, whereas heavily chargedfucoidan and bi-ligand neoglycoconjugate acted in converse manner.
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Reference: Ushakova N.A., Preobrazhenskaya M.E., Nifant'ev N.E., Usov A.I., Pochechueva T.V., Galanina O.E., Bovin N.V., Inhibitory activity of monomeric and polymeric selectin ligands, Voprosy meditsinskoi khimii, 1999, vol: 45(5), 375-383.
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