Inhibition of the type 1 fimbriae-mediated adhesion of Escherichia coli to erythrocytes by multiantennary α-mannosyl clusters:: The effect of multivalency
Inhibition of the type 1 fimbriae-mediated adhesion of Escherichia coli to erythrocytes by multiantennary α-mannosyl clusters:: The effect of multivalency
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DOI：
10.1023/a:1006920027641
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发表时间：
1998-06-01
影响因子：
3
通讯作者：
Krallmann-Wenzel, U
中科院分区：
文献类型：
--
作者：
Lindhorst, TK;Kieburg, C;Krallmann-Wenzel, U
研究了α -甘露糖基糖簇和糖树状大分子作为重组大肠杆菌HB101菌株1型（甘露糖特异性）菌毛的多价抑制剂。用微滴板测定豚鼠红细胞的血凝抑制作用。多价效应对分子中多达三个甘露糖基残基的影响是明显的，而较大的衍生物对与毛状碳水化合物结合域的结合没有明显的影响。测试的最佳糖簇达到已知的强效抑制剂pNPMan的结合效力(3)。研究结果支持了附着蛋白FimH上单价识别位点的观点，它可能最适合三糖大小的分子或暴露三个-甘露糖基残基的分子，如糖簇8。用硫脲桥接的α -甘露糖基簇获得的结果，具有明确的糖价，促进了1型菌毛凝集素高亲和力抑制剂的开发。
alpha-Mannosyl glycoclusters and glycodendrimers were tested as multivalent inhibitors of the type 1 (mannose-specific) fimbriae of a recombinant E. coli HB101 strain. Inhibition of haemagglutination of guinea pig erythrocytes was determined on microtiter plates. The effect of multivalency is pronounced for up to three mannosyl residues in the molecule, whereas larger derivatives do not have an appreciable effect on binding to the fimbrial carbohydrate binding domain. The best glycoclusters tested reach the binding potency of the known potent inhibitor pNPMan (3). The results support the idea of a monovalent recognition site at the adhesive protein FimH, which might best accommodate molecules with the size of a trisaccharide or those which expose up to three alpha-mannosyl residues, such as the glycocluster 8. The results obtained with the thiourea-bridged alpha-mannosyl clusters, possessing defined sugar valencies, facilitate the development of high affinity inhibitors of the fimbrial lectin on type 1 fimbriae.