Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues

• Verfasst von: Kelm, Sørge [VerfasserIn]
• Verfasst von: Brossmer, Reinhard [VerfasserIn]
• Verfasst von: Isecke, Rainer [VerfasserIn]
• Verfasst von: Groß, Hans Jürgen [VerfasserIn]
• Verfasst von: Strenge, Karen [VerfasserIn]
• Verfasst von: Schauer, Roland [VerfasserIn]
• Titel: Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues
• Verf.angabe: Sørge Kelm, Reinhard Brossmer, Rainer Isecke, Hans-Jürgen Gross, Karen Strenge, Roland Schauer
• E-Jahr: 1998
• Jahr: August 1998
• Umfang: 10 S.
• Fussnoten: Elektronische Reproduktion der Druck-Ausgabe 25. Dezember 2001 ; Gesehen am 26.06.2024
• Titel Quelle: Enthalten in: EJB
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1967
• Jahr Quelle: 1998
• Band/Heft Quelle: 255(1998), 3, Seite 663-672
• ISSN Quelle: 1432-1033
• DOI: doi:10.1046/j.1432-1327.1998.2550663.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: myelin-associated glycoprotein.
• Sach-SW: Sialic acid
• Sach-SW: sialoadhesin
• Sach-SW: siglecs
• Sach-SW: structure-function relationship
• K10plus-PPN: 1892233142

Abstract

The siglecs, formerly called sialoadhesins, are a family of I-type lectins binding to sialic acids on the cell surface. Five members of this family have been identified : sialoadhesin, myelin-associated glycoprotein (MAG), Schwann cell myelin protein (SMP), CD22 and CD33. We have investigated the relevance of substituents at position C-9 and in the N-acetyl group of N-acetylneuraminic acid, using a series of synthetic sialic-acid analogues either on resialylated human erythrocytes or as free α-glycosides in hapten inhibition. All five siglecs require the hydroxy group at C-9 for binding, suggesting hydrogen bonding of this substituent with the binding site. Remarkable differences were found among the proteins in their specificity for modifications of the N-acetyl group. Whereas sialoadhesin, MAG and SMP do not tolerate a hydroxy group as in N-glycolylneuraminic acid, they bind to halogenated acetyl residues. In the case of MAG, N-fluoroacetylneuraminic acid is bound about 17-fold better than N-acetylneuraminic acid. In contrast, human and murine CD22 both show good affinity for N-glycolylneuraminic acid, but only human CD22 bound the halogenated compounds. In conclusion, our data indicate that interactions of the hydroxy group at position 9 and the N-acyl substituent contribute significantly to the binding strength.