Sialyl-Lewis X

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CD15
)
Sialyl-Lewis X
Names
IUPAC name
(5-Acetamido-3,5-dideoxy-D-glycero-α-D-galacto-non-2-ulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-[α-L-fucopyranosyl-(1→3)]-N-acetyl-D-glucosamine
Systematic IUPAC name
(2S,4S,5R,6R)-5-Acetamido-2-{[(2S,3R,4S,5S,6R)-2-{[(2R,3R,4R,5R)-5-acetamido-1,2-dihydroxy-6-oxo-3-{[(2S,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}hexan-3-yl]oxy}-2,4-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy}-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
Other names
sialyl LeX, SLeX, CD15s, SSEA-1
Identifiers
3D model (
JSmol
)
ChEMBL
ChemSpider
MeSH sialyl+Lewis+X
UNII
  • InChI=1S/C31H52N2O23/c1-9-18(43)21(46)22(47)28(51-9)53-24(12(5-34)32-10(2)38)25(15(42)7-36)54-29-23(48)27(20(45)16(8-37)52-29)56-31(30(49)50)4-13(40)17(33-11(3)39)26(55-31)19(44)14(41)6-35/h5,9,12-29,35-37,40-48H,4,6-8H2,1-3H3,(H,32,38)(H,33,39)(H,49,50)/t9-,12-,13-,14+,15+,16+,17+,18+,19+,20-,21+,22-,23+,24+,25+,26+,27-,28-,29-,31-/m0/s1 checkY
    Key: LAQPKDLYOBZWBT-NYLDSJSYSA-N checkY
  • InChI=1/C31H52N2O23/c1-9-18(43)21(46)22(47)28(51-9)53-24(12(5-34)32-10(2)38)25(15(42)7-36)54-29-23(48)27(20(45)16(8-37)52-29)56-31(30(49)50)4-13(40)17(33-11(3)39)26(55-31)19(44)14(41)6-35/h5,9,12-29,35-37,40-48H,4,6-8H2,1-3H3,(H,32,38)(H,33,39)(H,49,50)/t9-,12-,13-,14+,15+,16+,17+,18+,19+,20-,21+,22-,23+,24+,25+,26+,27-,28-,29-,31-/m0/s1
    Key: LAQPKDLYOBZWBT-NYLDSJSYBC
  • O=C(N[C@@H]1[C@@H](O)C[C@](O[C@H]1[C@H](O)[C@H](O)CO)(O[C@@H]2[C@@H](O)[C@@H](O[C@H](CO)[C@@H]2O)O[C@@H]([C@H](O[C@@H]3O[C@H]([C@@H](O)[C@@H](O)[C@@H]3O)C)[C@H](C=O)NC(=O)C)[C@H](O)CO)C(=O)O)C
Properties
C31H52N2O23
Molar mass 820.744 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide

glycans
on the surface of cells. It is known to play a vital role in cell-to-cell recognition processes. It is also the means by which an egg attracts sperm; first, to stick to it, then bond with it and eventually form a zygote.

Sialyl Lewis X is also one of the most important

Th2 cells
.

Structure

Sialyl-Lewis X is a tetrasaccharide composed of a

N-acetyllactosamine. Its systematic name is 5-acetylneuraminyl-(2-3)-galactosyl-(1-4)-(fucopyranosyl-(1-3))-N-acetylglucosamine (Neu5Acα2-3Galβ1-4[Fucα1-3]GlcNAcβ). In humans, according to Table 1[1] and Fig.1[2] it is synthesized by four fucosyltransferases: FUT3, FUT5, FUT6 and FUT7. The other three enzymes of the sialyltransferase family ST3GAL3, ST3GAL4, and ST3GAL6 participate in the synthesis of the Sialyl-Lewis X precursor.[2]

Function

Leukocyte homing

Sialyl-Lewisx is important in leukocyte tethering and rolling. Leukocytes move through the blood stream and then tether themselves to the endothelial wall and roll along the endothelial tissue to determine if they want to leave the bloodstream to get to necessary tissue. Sialyl-Lewisx is a necessary partner for the three selectins that bind the leukocyte and endothelial cells. When sialyl-Lewisx is part of an O-glycan and attached to CD34 it can then bind to L-selectin. For the binding to L-selectin to occur sialyl-Lewisx must undergo sulfation. For sialyl-Lewisx to bind to P-selectin, an O-linked glycan near the N-terminus of P-Selectin Glycoprotein Ligand-1 (PSGL-1) is modified with sialyl-Lewisx and in combination with nearby tyrosine residues modified with sulfate, forms the binding contact for P-selectin. For sialyl-Lewisx to bind to E-selectin it can be part of either an N-linked or O-linked glycan attached to cell surface glycoproteins such as PSGL-1, CD43 or CD44. This sialyl-Lewisx mediated binding to selectins allows circulating leukocytes to stick to and roll along endothelial cells lining blood vessels thereby enabling the leukocytes to accumulate at a site of vascular inflammation.

Fertilization

Sialyl-Lewisx allows a sperm cell to recognize and fertilize an egg cell. For fertilization to occur, human sperm must bind to the zona pellucida (ZP), the translucent matrix covering the human egg composed of four glycoproteins ZP1, 2, 3, and 4, and transit through the matrix in order to fuse with the oocyte.[3] Human ZP is coated with highly dense N- and O-glycans that are terminated with the sialyl-Lewisx sequence.[4] The hemizona assay, which assesses sperm-ZP binding by counting the number of sperm bound to hemispheres of bisected nonliving human eggs in vitro, revealed that as little as 0.5 mM sialyl-Lewisx inhibits sperm-ZP binding by 63%.[4] Furthermore, adding purified and solubilized ZP3 or ZP4 from the human oocyte dose-dependently inhibits sperm-ZP binding in the hemizona assay.[5] Such evidence suggest that the early steps of human sperm-egg binding may be mediated by lectins for sialyl-Lewisx present on human sperm.

Clinical significance

Leukocyte adhesion deficiency

Main article: Congenital disorder of glycosylation type IIc

Defective synthesis of the sialyl Lewis X antigen results in immunodeficiency (leukocyte adhesion deficiency type 2). Defective synthesis can be caused by the loss of fucosyltransferase, impairing the glycosylation of the glycosphingolipid. Sialyl Lewis x is being researched for detection and treatment of immune disorders because of its presence on leukocytes.

Blood cancers

Sialyl-Lewisx mediates

CD45; the latter does not stain Reed-Sternberg cells, but does stain almost all other lymphoid cells. Sialyl-Lewisx is also present in about 50% of adenocarcinoma cells and can be used to distinguish such conditions from mesothelioma, which is typically negative.[7]

Cancer metastasis

Sialyl-Lewisx plays a critical role in cancer metastasis, facilitating the extravasation of cancer cells out of the bloodstream while they are moving through the body. Its expression is related to tumor stage, recurrence, and overall patient survival.[8] Therefore, sialyl Lewis x is being used as a target in studies to fight tumors and cancer cell growth. It has been shown that there is frequent overexpression of sialyl Lewis x on cancer cells and is found on both N-glycan and O-glycans. Sialyl Lewis x is being researched with CD markers to find new ways to create biosensors for cancer cells. Also, it is being used in new ways to target cancer cells specifically for cancer treatment.

In vitro fertilization

Further information:
In vitro fertilization

Sialyl-Lewisx is being used to achieve greater rates of fertilization of eggs in women by coating the eggs with sialyl Lewis x.

Immunity and inflammation

It plays a key role in the inflammatory response and may be used to increase the leukocyte response to infections. Sialyl Lewis x is also an inflammation-associated antigen on liver cells. It becomes over expressed on diseased liver cells and can be used as a way to detect liver disease in a patient.

MERS coronavirus binding

In June 2019, before the onset of the COVID-19 pandemic, the sulfated sialyl-Lewis X oligosaccharide (particularly with α2,3 linkages) receptor was found to be the preferred binding site, both in humans and in dromedary camels, for the coronavirus causing Middle East Respiratory Syndrome (MERS), the sixth coronavirus to be described.[9][10]

History

The term Lewis in its name comes from the name of a family of people who suffered from a red blood cell incompatibility. The studies done on these individuals' red blood cells led to the discovery of sialyl Lewis X. Sialyl Lewis x is a very important red blood cell antigen present on the glycolipids on the plasma membrane of the cell.

Its localization on the cell surface of cells led to its alternative nomenclature as a

monoclonal antibodies
. Sialyl Lewis X was assigned the name CD15.

See also

References

  1. PMID 11588153
    .
  2. ^
    PMID 28241499
    .
  3. PMID 23315069
    .
  4. ^
    S2CID 23610213
    .
  5. PMID 18667750
    .
  6. S2CID 8602651
    .
  7. ISBN 1-84110-100-1
    .
  8. PMID 27307752
    .
  9. PMID 31160783
    .
  10. S2CID 20912646
    .

Further reading
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