Roy R, Pagé D, Perez S F, Bencomo V V
Department of Chemistry, University of Ottawa, ON, Canada.
Glycoconj J. 1998 Mar;15(3):251-63. doi: 10.1023/a:1006945028547.
Clusters of di-, tri-, and tetra-antennary alpha-D-mannopyranosides were synthesized in good yields based on the coupling of amine-bearing mono- or trisaccharide [Man alpha(1 --> 6)[Man alpha(1 --> 3)]Man] haptens to poly-isocyanate or -isothiocyanate tethering cores. The relative binding properties of the resulting multivalent ligands were determined by turbidimetric and solid phase enzyme-linked lectin assays (ELLA) using plant lectins (phytohemagglutinins) Concanavalin A (Con A) and Pisum sativum (pea lectin) having four and two carbohydrate binding sites, respectively. Rapid and efficient cross-linking between tetravalent Con A and mannopyranosylated clusters were measured by a microtiter plate version of turbidimetric analyses. In inhibition of binding of the lectins to yeast mannan, the best tetravalent monosaccharide (30) and trisaccharide (31) inhibitors were shown to be 140 and 1155 times more potent inhibitors than monomeric methyl alpha-D-mannopyranoside against pea lectin and Con A, respectively. Compounds 30 and 31 were thus 35- and 289-fold more potent than the reference monosaccharide based on their hapten contents. As a general observation, the ligands bearing the Man alpha(1 --> 6)[Man alpha(1 --> 3)]Man trimannoside structures were found to be more potent inhibitors for Con A than the ligands having single mannoside residues, whereas pea lectin could not discriminate between the two types of ligands.
基于含胺的单糖或三糖[Manα(1→6)[Manα(1→3)]Man]半抗原与多异氰酸酯或异硫氰酸酯连接核心的偶联反应，以良好的产率合成了二天线、三天线和四天线的α-D-甘露吡喃糖苷簇。使用分别具有四个和两个碳水化合物结合位点的植物凝集素（植物血凝素）伴刀豆球蛋白A（Con A）和豌豆凝集素，通过比浊法和固相酶联凝集素分析（ELLA）测定所得多价配体的相对结合特性。通过比浊分析的微量滴定板版本测量四价Con A与甘露吡喃糖基化簇之间的快速有效交联。在抑制凝集素与酵母甘露聚糖的结合方面，最佳的四价单糖（30）和三糖（31）抑制剂对豌豆凝集素和Con A的抑制效力分别比单体甲基α-D-甘露吡喃糖苷高140倍和1155倍。基于其半抗原含量，化合物30和31的效力分别比参考单糖高35倍和289倍。一般观察发现，带有Manα(1→6)[Manα(1→3)]Man三甘露糖苷结构的配体对Con A的抑制作用比具有单个甘露糖苷残基的配体更强，而豌豆凝集素无法区分这两种类型的配体。
