Sialyl-Lewis X

{{DISPLAYTITLE:Sialyl-Lewis ^X}}{{More citations needed|date=November 2023}}{{chembox | verifiedrevid = 442085682 | ImageFile = Sialyl lewis x.svg | ImageSize = 250px | IUPACName = (5-Acetamido-3,5-dideoxy-<small>D</small>-''glycero''-α-<small>D</small>-''galacto''-non-2-ulopyranosylonic acid)-(2→3)-β-<small>D</small>-galactopyranosyl-(1→4)-[α-<small>L</small>-fucopyranosyl-(1→3)]-''N''-acetyl-<small>D</small>-glucosamine | SystematicName = (2''S'',4''S'',5''R'',6''R'')-5-Acetamido-2-{[(2''S'',3''R'',4''S'',5''S'',6''R'')-2-{[(2''R'',3''R'',4''R'',5''R'')-5-acetamido-1,2-dihydroxy-6-oxo-3-<nowiki/>{[(2''S'',3''S'',4''R'',5''S'',6''S'')-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-[(1''R'',2''R'')-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid | OtherNames = sialyl Le^X, SLe^X, CD15s, SSEA-1 |Section1={{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 559072 | 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 | InChIKey = LAQPKDLYOBZWBT-NYLDSJSYBC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = LAQPKDLYOBZWBT-NYLDSJSYSA-N | CASNo_Ref = {{cascite|correct|??}} | CASNo = 98603-84-0 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 0PS35WG8U3 | PubChem = 643990 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 375586 | SMILES = 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 | MeSHName = sialyl+Lewis+X }} |Section2={{Chembox Properties | Formula = C₃₁H₅₂N₂O₂₃ | MolarMass = 820.744 g/mol | Appearance = | Density = | MeltingPt = | BoilingPt = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}

'''Sialyl Lewis^X (sLeX)''', also known as '''cluster of differentiation 15s''' ('''CD15s''') or '''stage-specific embryonic antigen 1''' ('''SSEA-1'''), is a tetrasaccharide carbohydrate which is usually attached to O-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 blood group antigens and is displayed on the terminus of glycolipids that are present on the cell surface. The sialyl-Lewis^X determinant, E-selectin ligand carbohydrate structure, is constitutively expressed on granulocytes and monocytes and mediates inflammatory extravasation of these cells. Resting T and B lymphocytes lack its expression and are induced to strongly express sialyl-Lewis^X upon activation. The sialyl-Lewis^X determinant is expressed preferentially on activated T_h1 cells but not on T_h2 cells.

==Structure== Sialyl-Lewis^X is a tetrasaccharide composed of a sialic acid, fucose and an ''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,<ref>{{Cite journal|last1=de Vries|first1=T.|last2=Knegtel|first2=R. M.|last3=Holmes|first3=E. H.|last4=Macher|first4=B. A.|date=October 2001|title=Fucosyltransferases: structure/function studies|journal=Glycobiology|volume=11|issue=10|pages=119R–128R|doi=10.1093/glycob/11.10.119r|issn=0959-6658|pmid=11588153|doi-access=free}}</ref><ref name=":0">{{Cite journal|last1=Trinchera|first1=Marco|last2=Aronica|first2=Adele|last3=Dall’Olio|first3=Fabio|date=2017-02-23|title=Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers|journal=Biology|volume=6|issue=1|pages=16|doi=10.3390/biology6010016|issn=2079-7737|pmc=5372009|pmid=28241499|doi-access=free}}</ref> 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.<ref name=":0" />

==Function== ===Leukocyte homing=== Sialyl-Lewis^X 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 endothelium before potentially exiting into the tissue. Sialyl-Lewis^X is a necessary partner for the three selectins that bind the leukocyte and endothelial cells. When sialyl-Lewis^X 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-Lewis^X must undergo sulfation. For sialyl-Lewis^X 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-Lewis^X and, in combination with nearby tyrosine residues modified with sulfate, forms the binding contact for P-selectin. For sialyl-Lewis^X 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-Lewis^X-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-Lewis^X 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.<ref>{{Cite journal | last1 = Clark | first1 = G. F. | title = The role of carbohydrate recognition during human sperm-egg binding | doi = 10.1093/humrep/des447 | journal = Human Reproduction | volume = 28 | issue = 3 | pages = 566–577 | year = 2013 | pmid = 23315069| doi-access = free }}</ref> The human ZP is coated with dense N- and O-glycans that are terminated with the sialyl-Lewis^X sequence.<ref name="Pang">{{cite journal |last1=Pang |first1=Poh-Choo |last2=Chiu |first2=Philip C. N. |last3=Lee |first3=Cheuk-Lun |last4=Chang |first4=Lan-Yi |last5=Panico |first5=Maria |last6=Morris |first6=Howard R. |last7=Haslam |first7=Stuart M. |last8=Khoo |first8=Kay-Hooi |last9=Clark |first9=Gary F. |last10=Yeung |first10=William S. B. |last11=Dell |first11=Anne |display-authors=2 |date=18 August 2011 |title=Human Sperm Binding Is Mediated by the Sialyl-Lewisx Oligosaccharide on the Zona Pellucida |journal=Science |volume=333 |issue=6050 |pages=1761–1764 |bibcode=2011Sci...333.1761P |doi=10.1126/science.1207438 |pmid=21852454 |s2cid=23610213 |hdl-access=free |hdl=10044/1/15584}}</ref> The hemizona assay, which assesses sperm–ZP binding by counting the number of sperm bound to hemispheres of bisected nonliving human eggs ''in vitro'', reveals that 0.5 mM sialyl-Lewis^X inhibits sperm–ZP binding by 63%.<ref name="Pang" /> Furthermore, adding purified and solubilized ZP3 or ZP4 from the human oocyte dose-dependently inhibits sperm–ZP binding in the hemizona assay.<ref>{{Cite journal | last1 = Chiu | first1 = P. C. N. | last2 = Wong | first2 = B. S. T. | last3 = Chung | first3 = M. -K. | last4 = Lam | first4 = K. K. W. | last5 = Pang | first5 = R. T. K. | last6 = Lee | first6 = K. -F. | last7 = Sumitro | first7 = S. B. | last8 = Gupta | first8 = S. K. | last9 = Yeung | first9 = W. S. B. | doi = 10.1095/biolreprod.108.069344 | title = Effects of Native Human Zona Pellucida Glycoproteins 3 and 4 on Acrosome Reaction and Zona Pellucida Binding of Human Spermatozoa | journal = Biology of Reproduction | volume = 79 | issue = 5 | pages = 869–877 | year = 2008 | pmid = 18667750| doi-access = free }}</ref> Such evidence suggest that the early steps of human sperm–egg binding may be mediated by lectins for sialyl-Lewis^X present on human sperm.

==Clinical significance== ===Leukocyte adhesion deficiency=== {{Main|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-Lewis^X mediates phagocytosis and chemotaxis, found in neutrophils;<ref name="pmid1362195">{{cite journal |vauthors=Kerr MA, Stocks SC | title = The role of CD15-(Le(X))-related carbohydrates in neutrophil adhesion | journal = Histochem. J. | volume = 24 | issue = 11 | pages = 811–26 |date=November 1992 | pmid = 1362195 | doi = 10.1007/BF01046353| s2cid = 8602651 }}</ref> it is expressed by cells present in Hodgkin disease, some B-cell chronic lymphocytic leukemias, acute lymphoblastic leukemias, and most acute nonlymphocytic leukemias. CD15 is present on almost all Reed–Sternberg cells, including their rare mononuclear variants, and, as such, can be used in immunohistochemistry to identify the presence of such cells in biopsies. The presence of these cells is diagnostic of Hodgkin's lymphoma. Reed–Sternberg cells display a characteristic pattern of sialyl-Lewis^X positivity, with membranous staining combined with staining of the Golgi apparatus. Immunohistochemical panels for the diagnosis of Hodgkin's disease typically employ CD15 along with CD30 and CD45; the latter does not stain Reed–Sternberg cells, but does stain almost all other lymphoid cells. Sialyl-Lewis^X is also present in about 50% of adenocarcinoma cells and can be used to distinguish such conditions from mesothelioma, which is typically negative.<ref name=Leong>{{cite book|author=Leong, Anthony S-Y|author2=Cooper, Kumarason|author3=Leong, F Joel W-M|year=2003|title=Manual of Diagnostic Cytology|edition=2nd|publisher=Greenwich Medical Media, Ltd.|pages=83–84|isbn=1-84110-100-1}}</ref>

===Cancer metastasis=== Sialyl-Lewis^X plays a critical role in cancer metastasis, facilitating the extravasation of cancer cells out of the bloodstream when they are moving through the body. Its expression is related to tumor stage, recurrence, and overall patient survival.<ref>{{Cite journal|last1=Liang|first1=Jin-xiao|last2=Liang|first2=Yong|last3=Gao|first3=Wei|date=2016-05-24|title=Clinicopathological and prognostic significance of sialyl Lewis X overexpression in patients with cancer: a meta-analysis|journal=OncoTargets and Therapy|volume=9|pages=3113–3125|doi=10.2147/OTT.S102389|issn=1178-6930|pmc=4888715|pmid=27307752 |doi-access=free }}</ref> Therefore, sialyl Lewis x is being used as a target in studies to fight tumors and cancer cell growth. There is frequent overexpression of sialyl-Lewis^X on cancer cells, and it 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. It is also being used in new ways to target cancer cells specifically for cancer treatment.<ref name="d358">{{cite journal |last1=Szlasa |first1=Wojciech Kacper |last2=Sauer |first2=Natalia Julia |last3=Karwacki |first3=Jakub |last8=Malkiewicz |first8=Bartosz |date=2024-10-31 |title=Avelumab reduces STAT3 expression with effects on IL-17RA and CD15 |journal=Dental and Medical Problems |volume=61 |issue=5 |pages=713–720 |doi=10.17219/dmp/176374 |pmid=39480959 |issn=1644-387X |doi-access=free}}</ref>

===In vitro fertilization=== {{further|In vitro fertilization}} Sialyl-Lewis^X is being used to achieve greater rates of fertilization of eggs in women by coating the eggs with sialyl-Lewis^X.

===Immunity and inflammation=== Sialyl-Lewis^X 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 is overexpressed 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 receptor for sulfated sialyl-Lewis^X oligosaccharide (particularly with α2,3 linkages) 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.<ref>{{cite journal |last1=Tortorici |first1=M. Alejandra |last2=Walls |first2=Alexandra C. |last3=Lang |first3=Yifei |last4=Wang |first4=Chunyan |last5=Li |first5=Zeshi |last6=Koerhuis |first6=Danielle |last7=Boons |first7=Geert-Jan |last8=Bosch |first8=Berend-Jan |last9=Rey |first9=Félix A. |last10=de Groot |first10=Raoul J. |last11=Veesler |first11=David |title=Structural basis for human coronavirus attachment to sialic acid receptors |journal=Nature Structural & Molecular Biology |date=June 2019 |volume=26 |issue=6 |pages=481–489 |doi=10.1038/s41594-019-0233-y |pmid=31160783 |pmc=6554059 }}</ref><ref>{{cite journal |last1=Li |first1=Wentao |last2=Hulswit |first2=Ruben J. G. |last3=Widjaja |first3=Ivy |last4=Raj |first4=V. Stalin |last5=McBride |first5=Ryan |last6=Peng |first6=Wenjie |last7=Widagdo |first7=W. |last8=Tortorici |first8=M. Alejandra |last9=Dieren |first9=Brenda van |last10=Lang |first10=Yifei |last11=Lent |first11=Jan W. M. van |last12=Paulson |first12=James C. |last13=Haan |first13=Cornelis A. M. de |last14=Groot |first14=Raoul J. de |last15=Kuppeveld |first15=Frank J. M. van |last16=Haagmans |first16=Bart L. |last17=Bosch |first17=Berend-Jan |title=Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein |journal=Proceedings of the National Academy of Sciences |date=3 October 2017 |volume=114 |issue=40 |pages=E8508–E8517 |doi=10.1073/pnas.1712592114 |pmid=28923942 |pmc=5635925 |bibcode=2017PNAS..114E8508L |s2cid=20912646 |doi-access=free }}</ref>

==History== The term "Lewis" in the name comes from a family of people with 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 an important red blood cell antigen present on the glycolipids on the plasma membrane of the cell.

Its localization to the cell surface of cells led to its alternative nomenclature as a cluster of differentiation. Clusters of differentiation are a naming system devised in 1982 to classify cell-surface antigens on leukocytes identified via monoclonal antibodies. Sialyl-Lewis^X was assigned the name CD15.

== See also == * CA19-9 (sialyl-Lewis^A) * Lewis antigen

==References== {{reflist}}

==Further reading== * {{cite journal |last1=Chen |first1=G.-Y. |last2=Osada |first2=H. |last3=Santamaria-Babi |first3=L. F. |last4=Kannagi |first4=R. |title=Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes |journal=Proceedings of the National Academy of Sciences |date=7 November 2006 |volume=103 |issue=45 |pages=16894–16899 |doi=10.1073/pnas.0607926103 |pmid=17075044 |pmc=1629005 |bibcode=2006PNAS..10316894C |doi-access=free }} * {{cite journal |last1=Etzioni |first1=Amos |last2=Frydman |first2=Moshe |last3=Pollack |first3=Shimon |last4=Avidor |first4=Israeli |last5=Phillips |first5=M. Laurie |last6=Paulson |first6=James C. |last7=Gershoni-Baruch |first7=Ruth |title=Recurrent Severe Infections Caused by a Novel Leukocyte Adhesion Deficiency |journal=New England Journal of Medicine |date=17 December 1992 |volume=327 |issue=25 |pages=1789–1792 |doi=10.1056/NEJM199212173272505 |pmid=1279426 |doi-access=free }} * {{cite journal |last1=Sarangapani |first1=Krishna K. |last2=Qian |first2=Jin |last3=Chen |first3=Wei |last4=Zarnitsyna |first4=Veronika I. |last5=Mehta |first5=Padmaja |last6=Yago |first6=Tadayuki |last7=McEver |first7=Rodger P. |last8=Zhu |first8=Cheng |title=Regulation of Catch Bonds by Rate of Force Application |journal=Journal of Biological Chemistry |date=16 September 2011 |volume=286 |issue=37 |pages=32749–32761 |doi=10.1074/jbc.M111.240044 |pmid=21775439 |pmc=3173187 |doi-access=free }} * {{cite journal |last1=Pan |first1=Li-Hua |last2=Yamauchi |first2=Kohei |last3=Sawai |first3=Takashi |last4=Nakadate |first4=Toshihide |last5=Kojima |first5=Yuki |last6=Takahashi |first6=Naofumi |last7=Adachi |first7=Keisuke |last8=Kameyama |first8=Akihiko |last9=Inoue |first9=Hiroshi |title=Inhibition of Binding of E- and P-selectin to Sialyl-Lewis X Molecule Suppresses the Inflammatory Response in Hypersensitivity Pneumonitis in Mice |journal=American Journal of Respiratory and Critical Care Medicine |date=May 2000 |volume=161 |issue=5 |pages=1689–1697 |doi=10.1164/ajrccm.161.5.9812016 |pmid=10806176 }} * [https://www.ncbi.nlm.nih.gov/books/NBK453042/#_Ch14_s2_ Essentials of Glycobiology 3rd Edition, Chapter 14: "Structures Common to Different Glycans" https://www.ncbi.nlm.nih.gov/books/NBK453042/#_Ch14_s2_] * [http://www.chm.bris.ac.uk/motm/sla/sialyl.html Stephen J Isles, Molecule of the Month: Sialyl Lewis X]

{{Clusters of differentiation}} {{Clusters of differentiation by lineage}}

Category:Amino sugars Category:Tetrasaccharides Category:Acetamides Category:Clusters of differentiation Category:Human reproduction Category:Tumor markers