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A β-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.ijbiomac.2020.01.236
Hao Cui , Xinying Zhu , Zhengyi Huo , Bingbing Liao , Jingping Huang , Zhenxing Wang , Chunhui Song , Xiangguo Hu , Jianping Fang

Grifola frondosa is an edible and medicinal mushroom with great nutritional values and bioactivities. In the present study, a soluble homogeneous β-glucan, GFPS, with high molecular mass of 5.42 × 106 Da was purified from the fruit bodies of Grifola frondosa using 5% cold NaOH. The structure of GFPS was determined with FT-IR, NMR, and monosaccharide composition analysis, and was identified to be a β-D-(1-3)-linked glucan backbone with a single β-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue. Our results indicated that GFPS had a triple helical structure and could form complex with polydeoxyadenylic acid (poly[A]). Further studies demonstrated that GFPS could interact with poly[A] moiety of a designed antisense oligonucleotide (ASO) targeting the primary transcript of proinflammatory cytokine TNFα (TNFα-A60). This GFPS-based complex could incorporate TNFα-A60 into the macrophage cells via dectin-1 receptor and attenuate lipopolysaccharide-induced secretion of TNFα. Our results suggested that GFPS could be applied to deliver therapeutic oligonucleotides for the treatment of diseases such as inflammation and cancers.



中文翻译:

Grifola frondosa的β-葡聚糖可通过dectin-1受体有效地将治疗性寡核苷酸传递到细胞中并减弱TNFα基因的表达

Grifola frondosa是一种可食用的药用蘑菇,具有很高的营养价值和生物活性。在本研究中, 从Grifola frondosa的子实体中纯化了具有5.42×10 6 Da的高分子量的可溶性均质β-葡聚糖GFPS使用5%的冷NaOH。通过FT-IR,NMR和单糖组成分析确定GFPS的结构,并确定其为具有单个β-D-(1-6)-的β-D-(1-3)-连接的葡聚糖骨架。连接的吡喃葡萄糖基残基在每三个残基的C-6处分支。我们的结果表明,GFPS具有三重螺旋结构,可以与聚脱氧腺苷酸(poly [A])形成复合物。进一步的研究表明,GFPS可以与设计的反义寡核苷酸(ASO)的poly [A]部分相互作用,该寡核苷酸靶向促炎细胞因子TNFα(TNFα-A60)的主要转录本。这种基于GFPS的复合物可以通过dectin-1受体将TNFα-A60掺入巨噬细胞,并减弱脂多糖诱导的TNFα分泌。

更新日期:2020-01-24
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