DWI- Leibniz Institute for Interactive Materials, Institute of Technical and Macromolecular Chemistry RWTH Aachen University, Forckenbeckstraße 50, 52074, Aachen, Germany.
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA, 19104-6323, USA.
Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8352-8360. doi: 10.1002/anie.202100400. Epub 2021 Mar 4.
The effect of the two-dimensional glycan display on glycan-lectin recognition remains poorly understood despite the importance of these interactions in a plethora of cellular processes, in (patho)physiology, as well as its potential for advanced therapeutics. Faced with this challenge we utilized glycodendrimersomes, a type of synthetic vesicles whose membrane mimics the surface of a cell and offers a means to probe the carbohydrate biological activity. These single-component vesicles were formed by the self-assembly of sequence-defined mannose-Janus dendrimers, which serve as surrogates for glycolipids. Using atomic force microscopy and molecular modeling we demonstrated that even mannose, a monosaccharide, was capable of organizing the sugar moieties into periodic nanoarrays without the need of the formation of liquid-ordered phases as assumed necessary for rafts. Kinetics studies of Concanavalin A binding revealed that those nanoarrays resulted in a new effective ligand yielding a ten-fold increase in the kinetic and thermodynamic constant of association.
尽管糖-凝集素识别在众多细胞过程、（病理）生理学中具有重要意义，并且在先进治疗方面具有潜力，但二维聚糖展示对糖-凝集素识别的影响仍知之甚少。面对这一挑战，我们利用了糖脂囊泡，这是一种合成囊泡，其膜模拟了细胞表面，并提供了一种探测碳水化合物生物活性的方法。这些单一组分的囊泡是由序列定义的甘露糖 - 扬森树状聚合物自组装形成的，它们可以作为糖脂的替代品。使用原子力显微镜和分子建模，我们证明了即使是单糖甘露糖，也能够将糖基部分组织成周期性的纳米阵列，而无需形成液有序相，因为人们认为这对于筏子是必需的。伴刀豆球蛋白 A 结合的动力学研究表明，这些纳米阵列产生了一种新的有效配体，使结合的动力学和热力学常数增加了十倍。
