Institute of Organic and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225 Dusseldorf, Germany.
Biomacromolecules. 2020 Dec 14;21(12):4850-4856. doi: 10.1021/acs.biomac.0c01060. Epub 2020 Oct 13.
This study aims at quantifying the steric shielding effect of multivalent glycoconjugates targeting pathogens by blocking their carbohydrate binding sites. Specifically, PEGylated and non-PEGylated glycoconjugates are studied as inhibitors of lectins and bacterial adhesins evaluating the steric repulsion effect of the nonbinding PEG chains. We use the soft colloidal probe (SCP) adhesion assay to monitor the change in the adhesion energy of mannose (Man)-decorated hydrogel particles on a layer of concanavalin A (ConA) in the presence of sequence-defined multivalent glycoconjugate inhibitors over time. The results show that PEGylated glycoconjugates achieve a stronger adhesion inhibition when compared to non-PEGylated glycoconjugates although the dissociation constants () of the PEGgylated compounds to ConA were larger. These results appear in line with adhesion inhibition assays showing a small increase of bacteria detachment by PEGgylated glycoconjugates compared to non-PEGylated compounds. This suggests that an increase of sterical shielding via PEGylation may help reduce the invasiveness of pathogens even after they have adhered. Adhesion studies based on electrostatic interactions using amine-linked PEG of varying molecular weight confirm that such sterical shielding effect is not limited to carbohydrate-mediated adhesion.
本研究旨在通过阻断病原体的碳水化合物结合位点来量化多价糖缀合物的空间位阻屏蔽效应。具体而言，研究了聚乙二醇化和非聚乙二醇化的糖缀合物作为凝集素和细菌黏附素的抑制剂，评估了非结合 PEG 链的空间排斥效应。我们使用软胶体探针（SCP）黏附测定法来监测甘露糖（Man）修饰的水凝胶颗粒在存在序列确定的多价糖缀合物抑制剂时，随时间变化在层粘连蛋白 A（ConA）上的黏附能的变化。结果表明，与非聚乙二醇化糖缀合物相比，聚乙二醇化糖缀合物具有更强的黏附抑制作用，尽管聚乙二醇化化合物与 ConA 的解离常数（Kd）较大。这些结果与黏附抑制测定结果一致，表明与非聚乙二醇化化合物相比，PEG 化糖缀合物略微增加了细菌的脱落。这表明通过聚乙二醇化增加空间位阻屏蔽可能有助于降低病原体的侵袭性，即使它们已经黏附。使用不同分子量的胺连接 PEG 进行基于静电相互作用的黏附研究证实，这种空间位阻屏蔽效应不仅限于碳水化合物介导的黏附。
