Euzen Ronan, Reymond Jean-Louis
Technicians Training Laboratory, Institute of Chemical Sciences and Engineering (ISIC-GE), Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Mol Biosyst. 2011 Feb;7(2):411-21. doi: 10.1039/c0mb00177e. Epub 2010 Nov 1.
Glycodendrimers, such as glycoclusters and glycopolymers, are known to be very useful molecules to probe carbohydrate-lectin interactions. Herein, new second generation glycopeptide dendrimers (G2a-f) presenting a L-lysine-based (Lys) tetraantennary scaffold, four external thiomannosyl residues and, in the case of compounds G2b-f, four copies of a variable amino acid (X(1)) were synthesized and used as Concanavalin A (Con A) inhibitors. An increased-sensitivity Enzyme-Linked Lectin Assay (ELLA) was also developed to evaluate precisely the relative strength of the glycodendrimer-lectin interactions. Glycopeptide dendrimer G2e, for which L-tyrosine (Tyr) was used as a variable amino acid, led to optimal inhibition properties (IC(50) = 52 μM). Additionally, glycopeptide dendrimers G2g-k built on a scaffold displaying four external Tyr and more internally, four copies of a variable amino acid (X(2)) were synthesized and involved in the mentioned ELLA. Even if no strong improvement was observed, such structural modulations could also modify the inhibition properties of glycopeptide dendrimers. Finally, mono-, di- and octavalent analogs of G2e, noticed, respectively, G0, G1 and G3, were produced and assayed. Multivalency then appeared as a key feature since inhibition properties of these glycoconjuguates increased with the number of carbohydrate moieties and a relatively strong cluster effect was obtained for the octavalent derivative G3 (IC(50) = 2.9 μM).
糖树状大分子，如糖簇和糖聚合物，已知是用于探测碳水化合物 - 凝集素相互作用的非常有用的分子。在此，合成了具有基于L - 赖氨酸（Lys）的四天线支架、四个外部硫代甘露糖基残基的新型第二代糖肽树状大分子（G2a - f），并且对于化合物G2b - f而言，还含有四个可变氨基酸（X(1)）的拷贝，并用作伴刀豆球蛋白A（Con A）抑制剂。还开发了一种灵敏度增强的酶联凝集素测定法（ELLA）来精确评估糖树状大分子 - 凝集素相互作用的相对强度。使用L - 酪氨酸（Tyr）作为可变氨基酸的糖肽树状大分子G2e具有最佳抑制特性（IC(50) = 52 μM）。此外，合成了基于展示四个外部Tyr且在内部更多地含有四个可变氨基酸（X(2)）拷贝的支架的糖肽树状大分子G2g - k，并将其用于上述ELLA。即使未观察到显著改善，这种结构调节也可能改变糖肽树状大分子的抑制特性。最后，制备并测定了分别标记为G0、G1和G3的G2e的单价、二价和八价类似物。多价性随后表现为一个关键特征，因为这些糖缀合物的抑制特性随着碳水化合物部分数量的增加而增强，并且对于八价衍生物G3获得了相对较强的簇效应（IC(50) = 2.9 μM）。
