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Carbohydr Res. 2013 Sep 20;379:78-94. doi: 10.1016/j.carres.2013.06.011. Epub 2013 Jul 3.

Synthesis of a series of multivalent homo-, and heteroglycosides and their anti-adhesion activities.

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1
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Haidian District, Beijing 100191, PR China.

Abstract

Adhesion of leukocytes to endothelium plays an important role in inflammatory diseases. We previously found that the tetravalent lactoside Gu-4 was able to inhibit leukocyte-endothelial cell adhesion significantly and that CD11b was the target of Gu-4 on the surface of leukocytes. In this report, we aimed to explore the relationship between structural characteristics of glycoclusters and anti-adhesion activity. Using selective glycosylation method and convergent strategy, we synthesized a new series of homoglycoclusters and heteroglycoclusters with diverse structures. And the bioactivities of these compounds were assessed by a static state cell-based adhesion assay. We found that when the linked saccharide fragments are the same, the anti-adhesion activities of compounds with flexible linkers were stronger than those with rigid scaffold such as the benzene ring, and the best flexible linker in the tested compounds was L-glutamic acid. When l-glutamic acid was employed as the linker, glycoclusters with four valences, but not other valences, exhibited the most significant anti-adhesion activity; however, no significant differences in anti-adhesion activity were found among the tetravalentglycosides that were made by linking glucose (32), mannose (TMa-4), cellobiose (34), or lactose (Gu-4). Thus, we conclude that a flexible linker with proper length, such as that of L-glutamic acid, and the linking of four saccharide fragments might be the preferable structural characteristics for the glycocluster compounds with potent anti-adhesion activity.

KEYWORDS:

CD11b; Cell adhesion; Heteroglycocluster; Homoglycocluster; Synthesis

PMID:
23886987
DOI:
10.1016/j.carres.2013.06.011
[Indexed for MEDLINE]
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