| 张鹏,梁志赫,邹安琪,等.HNK-1化学酶法合成及其神经保护活性研究[J].中国海洋药物,2026,(1):-. |
| HNK-1化学酶法合成及其神经保护活性研究 |
| Chemoenzymatic synthesis of HNK-1 glycopolymers and study of their neuroprotective activities |
| 投稿时间：2024-04-18 修订日期：2025-02-17 |
| DOI： |
| 中文关键词: HNK-1 化学酶法合成 糖聚合物 ROMP RSC96细胞 |
| English Keywords:HNK-1 Chemoenzymatic synthesis Glycopolymer ROMP RSC96 cells |
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| 中文摘要: |
| 目的 利用化学酶法合成技术制备了系列HNK-1寡糖及其聚合物并对其神经保护活性进行初步研究,为周围神经损伤的治疗奠定基础。方法 以市售的溴代全乙酰化葡萄糖醛酸甲酯等为原料,通过化学酶法合成制备了系列HNK-1寡糖,并通过ROMP后修饰聚合策略制备了系列糖基聚合物,对糖聚合物进行了核磁氢谱、TEM、AFM、粒径电位等理化性质表征,并对糖聚合物的生物相容性和与相关受体蛋白的结合能力进行了初步评价。结果 经核磁共振波谱分析,证实糖聚合物的糖单元取代度分别为48%、45%和33%；通过TEM、AFM及马尔文粒度仪分析,系列糖聚合物的粒径在35 nm左右,Zeta电位显示糖聚合物都带有负电荷,且绝对值均大于25,证实该类化合物优良的稳定性。系列HNK-1寡糖及其聚合物都具有良好的细胞相容性,糖聚合物相比于寡糖,能够更好的促进RSC96细胞的增殖和迁移。此外,通过表面等离子体共振技术发现,糖聚合物由于其“多价效应”,可以与特异性受体蛋白有效结合,其中HNK-1糖聚合物P2与Cadherin-2的结合能力最好,结合常数KD值达到2.55 μM,显著强于普通HNK-1寡糖。结论 HNK-1寡糖及其糖聚合物具有稳定的结构,并且表现出良好生物活性,在治疗神经损伤方面有较好的应用潜力。 |
| English Summary: |
| Objective A series of HNK-1 oligosaccharides and their polymers were prepared by chemoenzymatic synthesis technique and their properties were preliminarily investigated to lay the foundation for the treatment of peripheral nerve injury.
Methods A series of HNK-1 oligosaccharides were prepared by chemoenzymatic synthesis using commercially available methyl bromo-per-acetylated glucuronide and other raw materials, and their glycopolymers were prepared by a post ring-opening metathesis polymerization (ROMP) strategy, and the physicochemical properties of the glycopolymers were characterized by 1H NMR spectroscopy, TEM, AFM, and particle-size potentials, and the biocompatibility of the glycopolymers and their ability of binding to the relevant receptor proteins were also evaluated.
Results The substitution degree of the carbohydrate units was identified by NMR analysis to be 48%, 45% and 33%, respectively. The particle size of the series of glycopolymers was analyzed by TEM, AFM and Malvern particle size meter. The particle sizes of glycopolymers were characterized to be around 35 nm. Their zeta potentials were all negatively charged and the absolute values were all greater than 25, which confirms the excellent stability of these compounds. Moreover, the series of HNK-1 oligosaccharides and their glycopolymers have good cytocompatibility, and the glycopolymers can better promote the proliferation and migration of RSC96 cells compared with the oligosaccharides. In addition, the surface plasmon resonance technique revealed that the glycopolymers could effectively bind to specific receptor proteins due to their "multivalent effects", among which the HNK-1 glycopolymer P2 possessed the best binding ability to Cadherin-2, with a binding constant of 2.55 μM, which was significantly stronger than that of normal HNK-1 oligosaccharides. oligosaccharides.
Conclusion HNK-1 oligosaccharides and their glycopolymers are structurally stable and exhibit good bioactivity with good potential for development in the treatment of nerve damage. |
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