Ligand Recognition by E-Selectin: Synthesis, Inhibitory Activity and Conformational Analysis of Bivalent Sialyl Lewis x Analogs

DeFrees, Shawn; Kosch, W.; Way, William; Paulson, James C.; Sabesan, Subramaniam; Halcomb, Randall L.; Huang, Dongmei; Ichikawa, Yoshitaka; Wong, Chi‐Huey

doi:10.1021/ja00106a008

Cited by 129 publications

(31 citation statements)

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“…E-selectin was the most sensitive to carbohydrate density of the three selectins. The elevation of binding levels at higher carbohydrate densities is consistent with other workers' findings that increasingly multivalent forms of sLe X are more potent inhibitors of selectin-mediated adhesion (25)(26)(27)(28).…”

Section: Discussionsupporting

confidence: 91%

Scintillation Proximity Assay for E-, P-, and L-Selectin Utilizing Polyacrylamide-Based Neoglycoconjugates as Ligands

Game¹,

Rajapurohit²,

Clifford³

et al. 1998

Analytical Biochemistry

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Section: Discussionsupporting

confidence: 91%

Scintillation Proximity Assay for E-, P-, and L-Selectin Utilizing Polyacrylamide-Based Neoglycoconjugates as Ligands

Game¹,

Rajapurohit²,

Clifford³

et al. 1998

Analytical Biochemistry

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“…Some published reports show that monovalent sLex tetrasaccharide is able to block the P-selectindependent accumulation of granulocytes in models involving lung inflammation or cardiac reperfusion (42,43). In vitro data suggests also that oligosaccharide constructs bearing two sLex groups (divalent sLex structures) are five times better inhibitors of E-selectin-dependent adhesion compared to monovalent sLex (44,45). Although the generation of very complex oligosaccharides has been difficult, enzyme-aided synthesis makes it possible at this time (28).…”

Section: Discussionmentioning

confidence: 99%

De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.

Turunen

Majuri

Seppo

et al. 1995

The Journal of Experimental Medicine

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SummaryAcute organ transplant rejection is characterized by a heavy lymphocyte infiltration. We have previously shown that alterations in the graft endothelium lead to increased lymphocyte traffic into the graft. Here, we demonstrate that lymphocytes adhere to the endothelium of rejecting cardiac transplants, but not to the endothelium of syngeneic grafts or normal hearts analyzed with the in vitro Stamper-Woodruff binding assay. Concomitant with the enhanced lymphocyte adhesion, the cardiac endothelium begins to de novo express sialyl Lewis a and sialyl Lewis x (sLea and sLex) epitopes, which have been shown to be sequences of L-selectin counterreceptors. The endothelium of allografts, but not that of syngeneic grafts or normal controls, also reacted with the L-selectin-immunoglobulin G fusion protein, giving further proof of inducible L-selectin counterreceptors. The lymphocyte adhesion to endothelium could be significantly decreased either by treating the iymphocytes with anti-L-selectin antibody HRL-1, or by treating the tissue sections with sialidase or anti-sLea or anti-sLex monoclonal antibodies. Finally, we synthetized enzymatically several members of the sLex family oligosaccharides and analyzed their ability to block lymphocyte adhesion to cardiac endothelium. The monovalent sLex (a tetramer), divalent sLex (a decamer), and tetravalent sLex (a 22-mer) could all significantly reduce lymphocyte binding, but the inhibition by the tetravalent sLex-construct was clearly superior to other members of the sLex family. The crucial control oligosaccharides, sialyl lactosamines lacking fucose but being otherwise similar to the members of sLex family, had no effect on lymphocyte binding.

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“…In lymphocyte adhesion, for example, Le a /Le x and related sialylated and sulfated oligosaccharide sequences are important ligands [6,7]. Methods for detailed characterization of these recognition motifs are important in modern structural cell biology to derive structure/function relationships, particularly in the postgenomic era, in order to understand posttranslational glycosylation and its function.…”

mentioning

confidence: 99%

“…In contrast to oligonucleotides and peptides, oligosaccharides can form branched structures and hence, a relatively simple set of monosaccharides can form a huge number of complex structures. A greater degree of structural complexity produced by branching is the norm for naturally occurring carbohydrates, and frequently a branched sequence carrying two or more recognition motifs are more potent [6,7]. Although the branching pattern can be identified in the mass spectra of some derivatized oligosaccharides [27], detailed assignment of a specific chain branch and its linkage to the core sugar residue often needs more specialized methods.…”

mentioning

confidence: 99%

Branching pattern and sequence analysis of underivatized oligosaccharides by combined MS/MS of singly and doubly charged molecular ions in negative-ion electrospray mass spectrometry

Chai

Lawson

Piskarev

2002

J. Am. Soc. Mass Spectrom.

122

129

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We previously reported that sequence and partial linkage information, including chain and blood-group types, of reducing oligosaccharides can be obtained from negative-ion electrospray CID MS/MS on a quadrupole-orthogonal time-of-flight instrument with high sensitivity and without derivatization (Chai, W.; Piskarev, V.; Lawson, A. M. Anal. Chem. 2001, 73, 651-657). In contrast to oligonucleotides and peptides, oligosaccharides can form branched structures that result in a greater degree of structural complexity. In the present work we apply negative-ion electrospray CID MS/MS to core-branching pattern analysis using nine 3,6-branched and variously fucosylated oligosaccharides based on hexasaccharide backbones LNH/LNnH as examples. The important features of the method are the combined use of CID MS/MS of singly and doubly charged molecular ions of underivatized oligosaccharides to deduce the branching pattern and to assign the structural details of each of the 3-and 6-branches. These spectra give complimentary structural information. In the spectra of [M Ϫ H] Ϫ , fragment ions from the 6-linked branch are dominant and those from the 3-linked branch are absent, while fragment ions from both branches occur in the spectra of [M Ϫ 2H] 2Ϫ. This allows the distinction of fragment ions derived from either the 3-or 6-branches. In addition, a unique D 2␤-3 ion, arising from double D-type cleavage at the 3-linked glycosidic bond of the branched Gal core residue, provides direct evidence of the branching pattern with sequence and partial linkage information being derived from C-and A-type fragmentations, respectively. (J Am Soc Mass Spectrom 2002, 13, 670 -679) © 2002 American Society for Mass Spectrometry T he potential role of carbohydrates in cellular events has long been hypothesized although evidence for this has only strongly emerged over the last two decades. Awareness of the biological function of oligosaccharide chains in glycoproteins, glycolipids, and proteoglycans has intensified as an increasing number of examples have been reported which reveal that carbohydrate structures participate in various biological events as well as modifying protein functions. One of the early indications of carbohydrates in recognition was binding of the influenza virus to red blood cells via sialic acid [1], and later by work on the chemical basis of the antigenicity of polysaccharides and of the well-known ABO (H) bloodgroup system [2,3] in which specificity is determined by oligosaccharides. Carbohydrates are well placed to act in cellular recognition as many cells are surrounded by an oligosaccharide layer from cell associated glyco-

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Ligand Recognition by E-Selectin: Synthesis, Inhibitory Activity and Conformational Analysis of Bivalent Sialyl Lewis x Analogs

Cited by 129 publications

References 0 publications

Scintillation Proximity Assay for E-, P-, and L-Selectin Utilizing Polyacrylamide-Based Neoglycoconjugates as Ligands

Scintillation Proximity Assay for E-, P-, and L-Selectin Utilizing Polyacrylamide-Based Neoglycoconjugates as Ligands

De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.

Branching pattern and sequence analysis of underivatized oligosaccharides by combined MS/MS of singly and doubly charged molecular ions in negative-ion electrospray mass spectrometry

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