Ehrmann Svenja, Chu Chih-Wei, Kumari Shalini, Silberreis Kim, Böttcher Christoph, Dernedde Jens, Ravoo Bart Jan, Haag Rainer
Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
J Mater Chem B. 2018 Jul 7;6(25):4216-4222. doi: 10.1039/c8tb00922h. Epub 2018 May 29.
A supramolecular toolbox approach for multivalent ligand-receptor recognition was established based on β-cyclodextrin vesicles (CDVs). A series of bifunctional ligands for CDVs was synthesised. These ligands comprise on one side adamantane, enabling the functionalisation of CDVs with these ligands, and either mannose or sulphate group moieties on the other side for biological receptor recognition. The physicochemical properties of the host-guest complexes formed by β-cyclodextrin (β-CD) and adamantane were determined by isothermal titration calorimetry (ITC). Ligand-lectin interactions were investigated by surface plasmon resonance experiments (SPR) for the mannose ligands and the lectin Concanavalin A (ConA). Microscale thermophoresis (MST) measurements were applied for sulphate-dependent binding to L-selectin. In both cases, a multivalent affinity enhancement became apparent when the ligands were presented on the CDV scaffold. Furthermore, not only the clustering between our supramolecular mannosylated complex and Escherichia coli (E. coli), expressing the lectin FimH, was visualised by cryo-TEM, but also the competitive character to detach bound E. coli from a cell line, representing the uroepithelial cell surface, was demonstrated. In summary, a facile and effective supramolecular toolbox was established for various ligand-receptor recognition applications.
基于β-环糊精囊泡（CDV）建立了一种用于多价配体-受体识别的超分子工具箱方法。合成了一系列用于CDV的双功能配体。这些配体一侧包含金刚烷，可实现CDV与这些配体的功能化，另一侧为甘露糖或硫酸根基团部分，用于生物受体识别。通过等温滴定量热法（ITC）测定了β-环糊精（β-CD）与金刚烷形成的主客体复合物的物理化学性质。通过表面等离子体共振实验（SPR）研究了甘露糖配体与凝集素伴刀豆球蛋白A（ConA）之间的配体-凝集素相互作用。应用微量热泳动（MST）测量来研究硫酸盐依赖性与L-选择素的结合。在这两种情况下，当配体呈现在CDV支架上时，多价亲和力增强变得明显。此外，不仅通过冷冻透射电子显微镜（cryo-TEM）观察到我们的超分子甘露糖化复合物与表达凝集素FimH的大肠杆菌（E. coli）之间的聚集，而且还证明了从代表尿上皮细胞表面的细胞系中分离结合的大肠杆菌的竞争特性。总之，建立了一种简便有效的超分子工具箱，用于各种配体-受体识别应用。
