| Autor: |
Ushakova, N., Preobrazhenskaya, M., Bird, M., Priest, R., Semenov, A., Mazurov, A., Nifantiev, N., Pochechueva, T., Galanina, O., Bovin, N. |
| Předmět: |
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| Zdroj: |
Biochemistry (00062979); Apr2005, Vol. 70 Issue 4, p432-439, 8p |
| Abstrakt: |
The potency of the oligosaccharides SiaLex, SiaLea, HSO3Lex, and HSO3Lea, their conjugates with polyacrylamide (PAA, 40 kD), and other monomeric and polymeric selectin inhibitors has been compared with that of the polysaccharide fucoidan. The following assay systems were used: 1) a 96-well assay based either on the use of recombinant E-, P-, and L- selectins or an analogous assay with natural P-selectin isolated from human platelets; 2) a platelet-based P-selectin cell assay; and 3) a rat model of peritoneal inflammation. IC50 values for the neoglycoconjugate SiaLea-PAA were 6, 40, and 85 µM for recombinant E-, P-, and L-selectins, respectively; all monomeric inhibitors were about two orders of magnitude weaker. PAA-conjugates, containing as a ligand tyrosine-O-sulfate (sTyr) in addition to one of the sialylated oligosaccharides, were the most potent synthetic blockersin vitro. Compared with fucoidan, the most potent known P- and L-selectin blocker, the bi-ligand glycoconjugate HSO3Lea-PAA-sTyr displayed similar inhibitory activityin vitrotowards L-selectin and about ten times lower activity towards P-selectin. All of the tested synthetic polymers displayed a similar ability to inhibit neutrophil extravasation in the peritonitis model (in vivo) at 10 mg/kg. The data provide evidence that monomeric SiaLex is considerably more effective as a selectin blockerin vivothanin vitro, whereas the opposite is true for fucoidan and the bi-ligand neoglycoconjugate HSO3Lea-PAA-sTyr. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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