Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2→1] poly(fructo-furanosyl) α-D-glucose polymers
Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2→1] poly(fructo-furanosyl) α-D-glucose polymers
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DOI：
10.1093/glycob/cwq201
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发表时间：
2011-05-01
期刊：
影响因子：
4.3
通讯作者：
Petrovsky, Nikolai
中科院分区：
文献类型：
--
作者：
Cooper, Peter D.;Petrovsky, Nikolai
我们报道了一种新的β-D-[2 -> 1]聚（果糖-呋喃糖基）α-D-葡萄糖异构体，称为δ菊粉（DI），将其与先前描述的α（AI），β（BI）和γ（GI）异构体进行比较。在体外，DI在人补体活化和与单核细胞结合以及调节其趋化因子产生和细胞表面蛋白表达方面是最具免疫活性的重量/重量。在体内，这转化为有效的免疫佐剂活性，增强针对共同施用抗原的体液和细胞应答。作为生物相容性多糖颗粒，DI通过皮下或肌内注射是安全的且耐受性良好。在物理化学上，DI从保持在37-48摄氏度的合适的Al、BI或GI的水溶液中形成为不溶性沉淀物，而在较低温度下来自相同溶液的沉淀物具有Al或GI的性质。DI也可以通过GI悬浮液在56 ℃下的热转化来产生，而GI是在45 ℃下由AI转化而来的。DI与GI的区别在于其在稀水性悬浮液中的较高温度的溶液和其在二甲基亚砜中的较低溶解度，这两者与DI的聚合物填充结构中的较大氢键合一致。DI悬浮液可以通过加热溶解，通过冷却作为Al再沉淀，并最终通过重复热处理再转化回DI。因此，DI，如先前描述的菊粉同种型，反映了通过可逆的非共价键合形成不同的聚合物聚集体堆积结构。DI形成了一种有效的新型人类疫苗佐剂的基础，并进一步扩大了具有免疫活性的碳水化合物结构的不断增长的家族。
We report a novel isoform of beta-D-[2 -> 1] poly(fructo-furanosyl) alpha-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48 degrees C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56 degrees C, whereas GI is converted from AI at 45 degrees C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.