Zhang Ruiyan, Loers Gabriele, Schachner Melitta, Boelens Rolf, Wienk Hans, Siebert Simone, Eckert Thomas, Kraan Stefan, Rojas-Macias Miguel A, Lütteke Thomas, Galuska Sebastian P, Scheidig Axel, Petridis Athanasios K, Liang Songping, Billeter Martin, Schauer Roland, Steinmeyer Jürgen, Schröder Jens-Michael, Siebert Hans-Christian
RI-B-NT: Research Institute of Bioinformatics and Nanotechnology, Franziusallee 177, 24148, Kiel, Germany.
Zoological Institute, Department of Structural Biology, Kiel University, Am Botanischen Garten 1-9, 24118, Kiel, Germany.
ChemMedChem. 2016 May 6;11(9):990-1002. doi: 10.1002/cmdc.201500609. Epub 2016 May 2.
Polysialic acid (polySia) and polySia glycomimetic molecules support nerve cell regeneration, differentiation, and neuronal plasticity. With a combination of biophysical and biochemical methods, as well as data mining and molecular modeling techniques, it is possible to correlate specific ligand-receptor interactions with biochemical processes and in vivo studies that focus on the potential therapeutic impact of polySia, polySia glycomimetics, and sulfated polysaccharides in neuronal diseases. With this strategy, the receptor interactions of polySia and polySia mimetics can be understood on a submolecular level. As the HNK-1 glycan also enhances neuronal functions, we tested whether similar sulfated oligo- and polysaccharides from seaweed could be suitable, in addition to polySia, for finding potential new routes into patient care focusing on an improved cure for various neuronal diseases. The knowledge obtained here on the structural interplay between polySia or sulfated polysaccharides and their receptors can be exploited to develop new drugs and application routes for the treatment of neurological diseases and dysfunctions.
聚唾液酸（polySia）和聚唾液酸糖模拟分子可促进神经细胞再生、分化以及神经元可塑性。通过结合生物物理和生化方法，以及数据挖掘和分子建模技术，能够将特定的配体-受体相互作用与生化过程以及体内研究相关联，这些体内研究聚焦于聚唾液酸、聚唾液酸糖模拟物和硫酸化多糖在神经疾病中的潜在治疗作用。运用此策略，可在亚分子水平上理解聚唾液酸和聚唾液酸模拟物的受体相互作用。由于HNK-1聚糖也能增强神经元功能，我们测试了除聚唾液酸外，来自海藻的类似硫酸化寡糖和多糖是否也适合用于寻找潜在的新途径，以改善针对各种神经疾病的治疗从而为患者提供更好的护理。在此获得的关于聚唾液酸或硫酸化多糖与其受体之间结构相互作用的知识，可用于开发治疗神经疾病和功能障碍的新药及应用途径。
