title: Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues.
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 alpha-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.
authors.affiliation: Institute of Biochemistry, University of Kiel, Germany. skelm@biochem.uni-kiel.de
authors.forename: S
authors.initials: S
authors.lastname: Kelm
authors.forename: R
authors.initials: R
authors.lastname: Brossmer
authors.forename: R
authors.initials: R
authors.lastname: Isecke
authors.forename: H J
authors.initials: HJ
authors.lastname: Gross
authors.forename: K
authors.initials: K
authors.lastname: Strenge
authors.forename: R
authors.initials: R
authors.lastname: Schauer
mesh_terms: D001665:Binding Sites; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids