Inhibition of the adherence of cholera toxin and the heat-labile enterotoxin of Escherichia coli to cell-surface GM1 by oligosaccharide-derivatized dendrimers.
Inhibition of the adherence of cholera toxin and the heat-labile enterotoxin of Escherichia coli to cell-surface GM1 by oligosaccharide-derivatized dendrimers.
复制标题
寡糖衍生树枝状聚合物抑制霍乱毒素和大肠杆菌不耐热肠毒素对细胞表面 GM1 的粘附。
DOI：
10.1016/s0006-2952(98)00198-1
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发表时间：
1998
影响因子：
5.8
通讯作者：
Schengrund,CL
中科院分区：
文献类型：
--
作者：
Thompson,JP;Schengrund,CL
霍乱毒素或不耐热肠毒素与肠粘膜上皮细胞表面的单唾液酸神经节苷脂Gal(β1-3)GalNAc(β1-4)[唾液酸(α2-3)]Gal(β1-4)Glcβ1-神经酰胺(Gm1)的黏附是导致水样腹泻的一系列过程的第一步。虽然霍乱更严重，但两者都可能因脱水而导致死亡。通过将GAL(β1-3)GalNAc(β1-4)[唾液酸(α2-3)]GLc(β1-4)的多个苯基异硫氰酸酯(PITC)衍生物共价连接到聚丙烯亚胺树枝状大分子的臂上，以确定其作为这些疾病的治疗剂的潜力，测定了它们抑制毒素与细胞表面相关的GM1黏附的能力。它们不仅在5°时抑制霍乱毒素结合亚基(霍乱毒素结合亚单位)与GM1处理的NCTC-2071细胞(经化学转化的小鼠成纤维细胞)结合，而且在37°时抑制霍乱毒素、霍乱毒素和不耐热肠毒素与GM1处理的NCTC-2071细胞的黏附。观察毒素是在加入细胞之前与寡聚GM1-PITC衍生的树突状大分子预先孵育，还是在将衍生的树突状大分子加入细胞后立即给予抑制。台盼蓝拒染法检测，衍生化树枝状大分子对细胞存活率无影响。将霍乱毒素、霍乱全毒素或不耐热的大肠杆菌肠毒素与寡聚GM1-PITC衍生的树枝状大分子粘连引起的色氨酸荧光发射光谱最大值蓝移与粘连GM1或寡聚GM1引起的蓝移相似。当毒素与不起受体作用的神经节苷脂孵育时，没有观察到类似的变化。
The adherence of either cholera toxin or the heat-labile enterotoxin of Escherichia coli to monosialoganglioside gal(β1–3)galNAc(β1–4)[sialic acid (α2–3)]gal(β1–4)glcβ1–ceramide (GM1) present on the surface of epithelial cells lining the intestine is the first step of a series that results in the induction of a watery diarrhea. While cholera is more severe, both can lead to death as a result of dehydration. To determine the potential of defined multivalent oligosaccharides, synthesized by the covalent attachment of multiple phenylisothiocyanate (PITC) derivatives of gal(β1–3)galNAc(β1–4)[sialic acid(α2–3)]gal(β1–4)glc (oligo-GM1) to the arms of a poly(propylene imine) dendrimer, as therapeutic agents for these diseases, their ability to inhibit adherence of the toxins to cell surface-associated GM1 was determined. They not only inhibited choleragenoid (binding subunit of cholera toxin) binding to GM1-treated NCTC-2071 cells (chemically transformed murine fibroblasts) at 5°, but also inhibited adherence of the choleragenoid, cholera toxin, and heat-labile enterotoxin of E. coli to GM1-treated NCTC-2071 cells at 37°. Inhibition was observed whether the toxin was preincubated with the oligo-GM1-PITC-derivatized dendrimer prior to addition to cells or given just after the addition of the derivatized dendrimer to cells. The derivatized dendrimer had no effect on cell viability, as monitored by trypan blue exclusion. Blue-shifts in tryptophan fluorescence emission spectra maxima induced by adherence of either choleragenoid, cholera holotoxin, or the heat-labile enterotoxin of E. coli to oligo-GM1-PITC-derivatized dendrimers were similar to those induced by adherence to GM1 or oligo-GM1. Comparable shifts were not observed when the toxins were incubated with gangliosides that fail to function as receptors.