High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction.
High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction.
复制标题
DOI：
10.3762/bjoc.8.91
复制
发表时间：
2012
影响因子：
2.7
通讯作者：
Wittmann V
中科院分区：
文献类型：
--
作者：
Beckmann HS;Möller HM;Wittmann V
以市售胺为原料，采用一锅法合成了六个N，N‘-二乙酰基甲壳二糖的一价、二价和三价衍生物。以共价固定化N-乙酰氨基葡萄糖(GlcNAc)为参比配体，用酶联凝集素测定法(ELLA)研究了这些糖簇与普通小麦植物凝集素麦芽凝集素(WGA)的结合能力。IC50值在低微摩尔/高纳米摩尔范围内，这取决于两个双糖之间的连接物。与N，N‘-二乙酰基壳二糖作为相应的单价配体相比，观察到二价配体的结合增强β高达1000，三价WGA配体的结合增强达2800。分子模拟研究中，甲壳二糖部分被拟合到结晶学确定的WGA的结合位置，将多价配体的结合增强与它们以螯合模式与蛋白质结合的能力相关联。最好的WGA配体是三价簇，其IC50值为220 nm。按所含甲壳二糖的摩尔计算，这是迄今为止已知的最好的WGA配体。
A series of six mono-, di-, and trivalent N,N’-diacetylchitobiose derivatives was conveniently prepared by employing a one-pot procedure for Cu(II)-catalyzed diazo transfer and Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) starting from commercially available amines. These glycoclusters were probed for their binding potencies to the plant lectin wheat germ agglutinin (WGA) from Triticum vulgaris by an enzyme-linked lectin assay (ELLA) employing covalently immobilized N-acetylglucosamine (GlcNAc) as a reference ligand. IC50 values were in the low micromolar/high nanomolar range, depending on the linker between the two disaccharides. Binding enhancements β up to 1000 for the divalent ligands and 2800 for a trivalent WGA ligand, compared to N,N’-diacetylchitobiose as the corresponding monovalent ligand, were observed. Molecular modeling studies, in which the chitobiose moieties were fitted into crystallographically determined binding sites of WGA, correlate the binding enhancements of the multivalent ligands with their ability to bind to the protein in a chelating mode. The best WGA ligand is a trivalent cluster with an IC50 value of 220 nM. Calculated per mol of contained chitobiose, this is the best WGA ligand known so far.
登录
查看更多内容
影响因子：
--
作者：
Corbell, JB;Lundquist, JJ;Toone, EJ
通讯作者：
Toone, EJ
影响因子：
4.7
作者：
Andre, Sabine;Specker, Daniel;Wittmann, Valentin
通讯作者：
Wittmann, Valentin
影响因子：
2.9
作者：
BAINS, G;LEE, RT;FREIRE, E
通讯作者：
FREIRE, E
影响因子：
15
作者：
Kitov, PI;Bundle, DR
通讯作者：
Bundle, DR
影响因子：
15
作者：
Gargano, JM;Ngo, T;Lees, WJ
通讯作者：
Lees, WJ