Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues
Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues
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DOI：
10.1046/j.1432-1327.1998.2550663.x
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发表时间：
1998-08-01
期刊：
影响因子：
--
通讯作者：
Schauer, R
中科院分区：
文献类型：
--
作者：
Kelm, S;Brossmer, R;Schauer, R
siglecs，以前称为唾液酸粘附素，是与细胞表面唾液酸结合的 I 型凝集素家族。该家族的五个成员已被鉴定：唾液酸粘附素、髓磷脂相关糖蛋白 (MAG)、雪旺细胞髓磷脂蛋白 (SMP)、CD22 和 CD33。我们研究了 C-9 位取代基和 N-乙酰神经氨酸的 N-乙酰基中的取代基的相关性，使用一系列合成的唾液酸类似物，或者在再唾液酸化的人红细胞上，或者作为半抗原抑制中的游离 α-糖苷。所有五个 siglec 都需要 C-9 处的羟基进行结合，表明该取代基与结合位点形成氢键。蛋白质对 N-乙酰基修饰的特异性存在显着差异。尽管唾液酸粘附素、MAG 和 SMP 不能耐受 N-乙醇酰神经氨酸中的羟基，但它们会与卤代乙酰基残基结合。就 MAG 而言，N-氟乙酰神经氨酸的结合效果是 N-乙酰神经氨酸的约 17 倍。相比之下，人和鼠CD22都对N-乙醇酰神经氨酸表现出良好的亲和力，但只有人CD22结合卤代化合物。总之，我们的数据表明，9 位羟基和 N-酰基取代基的相互作用对结合强度有显着影响。
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 a-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.