Oligosaccharide recognition by selectins: Synthesis and biological activity of multivalent sialyl lewis-X ligands

Kretzschmar, Gerhard; Sprengard, Ulrich; Kunz, Horst; Bartnik, Eckart; Schmidt, Wolfgang; Toepfer, Alexander; Hörsch, Brigitte; Krause, Manfred; Seiffge, D.

doi:10.1016/0040-4020(95)00833-t

Cited by 66 publications

(26 citation statements)

References 41 publications

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“…[14] Therefore, various research groups have prepared synthetic sLe X clusters, but these studies could only in part support this hypothesis of increased affinity. [15,16] Furthermore, the extended flexible structure of the sialomucins is thought to be essential for the mediation of cell rolling. However, lipid based sLe X molecules (glycosphingolipids) at the leukocyte surface, as well as selectin ligands, have been postulated to act in the rolling process.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Sialyl Lewis X Epitope Attached to Glycolipids with Different Core Structures and their Selectin-Binding Characteristics in a Dynamic Test System

et al. 2000

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Sialyl Lewis X (sLeX)/selectin-mediated leukocyte rolling along endothelial cells has recently gained wide interest. In this paper the influence of the spacer length of laterally clustered neoglycolipids 1a-d on cell rolling in a dynamic test system is investigated. The required di-O-hexadecyl glycerols with none, and with three, six, or nine ethylene glycol units as spacer groups (compounds 4a-d) could be readily obtained. The synthesis of 1-O-thexyldimethylsilyl-protected sLeX 24 was based on sialylation of 2,3,4-O-unprotected galactose derivative 11 with sialyl phosphite 8 as donor; this afforded the desired disaccharide 12, which was transformed into trichloroacetimidate 14 as disaccharide donor. Reaction of 3-O-unprotected glucosamine derivative 18 with fucosyl donor 20 afforded disaccharide 21, which was transformed into the 4-O-unprotected derivative 23. Reaction of 14 with 23 furnished the desired tetrasaccharide 24 in good yield. Transformation of 24 into the trichloroacetimidate 26 as donor, followed by the reaction with 4a-d as acceptor gave, after deprotection, the target molecules 1a-d. For comparison, 4d was also connected with a sialyl residue (-->31) and with an N-acetylglucosamine residue (-->34). Compounds 1c and 1d with a hexaethylene glycol and a nonaethylene glycol spacer, respectively, were much more efficient in mediating selectin-dependent cell rolling in the dynamic test system than compounds 1a and 1b, which had no spacer (1a), or only a triethylene glycol spacer (1b).

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Section: Introductionmentioning

confidence: 99%

Synthesis of the Sialyl Lewis X Epitope Attached to Glycolipids with Different Core Structures and their Selectin-Binding Characteristics in a Dynamic Test System

et al. 2000

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“…[9,10] As follows, the main task in the synthesis of fluorescent conjugate 2 was to develop an efficient route to 3,6-diglycosylated galactosyl azides.…”

Section: Resultsmentioning

confidence: 99%

“…Studies involving bi-, [5±8, 18] tri-, [7,9,10] tetra-, [11] and polyvalent [12±17] sLe x derivatives have suggested that the selectin ± ligand interaction may be multivalent in nature.…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis and Fluorescent Visualization of Cell-Surface Selectin-Bound Sialyl Lewis X Derivatives

Wittmann¹,

Datta²,

Koeller³

et al. 2000

Chem. Eur. J.

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Sialyl Lewis x (sLe(x)) derivatives conjugated to readily visualized molecular labels are useful chemical probes to study selectin-carbohydrate interactions. Localization of the selectins on the surface of leukocytes and activated endothelial cells can be detected through fluorescence of bound selectin ligands. Herein we present a short chemoenzymatic synthesis of a fluorescently labeled bivalent sLe(x) conjugate. The use of an amino-substituted monovalent sLe(x) to obtain fluorescent- and biotin-labeled sLe(x) derivatives is also described. The cell-staining utility of the fluorescent sLe(x) conjugates is demonstrated for a HUVEC cell line expressing E-selectin and for CHO-K1 cells expressing either L- or E-selectin.

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“…Kretzschmar et al synthesized trivalent Sialyl-Lewis(x) ligands, and showed inhibition of E-selectin and P-selectin mediated cell adhesion both in vitro and in vivo. [63] Autoimmunity: The immune system employs many processes to ensure that self-reactive B-cells and T-cells are eliminated. Failure of these processes leads to autoimmunity, and combating self-reactive immune cells can be challenging.…”

Section: Anti-inflammationmentioning

confidence: 99%

The Design of Polyvalent Therapeutics

Joshi

Vance

Rai

et al. 2008

Chemistry A European J

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Oligosaccharide recognition by selectins: Synthesis and biological activity of multivalent sialyl lewis-X ligands

Cited by 66 publications

References 41 publications

Synthesis of the Sialyl Lewis X Epitope Attached to Glycolipids with Different Core Structures and their Selectin-Binding Characteristics in a Dynamic Test System

Synthesis of the Sialyl Lewis X Epitope Attached to Glycolipids with Different Core Structures and their Selectin-Binding Characteristics in a Dynamic Test System

Chemoenzymatic Synthesis and Fluorescent Visualization of Cell-Surface Selectin-Bound Sialyl Lewis X Derivatives

The Design of Polyvalent Therapeutics

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