p-(succinylamido)phenyl β-D-glucopyranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: p-(succinylamido)phenyl β-D-glucopyranoside
• 英文别名: 4-oxo-4-[4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanilino]butanoic acid
• 化学式: C₁₆H₂₁NO₉
• 分子量: 371.344
• InChiKey: PEZVCPCKMXHCJO-LMXXTMHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  二甲基硫代磷酰氯 、 甘氨酰甘氨酰酪氨酰-精氨酸 、 p-(succinylamido)phenyl β-D-glucopyranoside 在 三正丁胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Improvement of Intestinal Absorption of Peptide Drugs by Glycosylation: Transport of Tetrapeptide by the Sodium Ion-Dependent D-Glucose Transporter

  摘要：

  A tetrapeptide (Gly-Gly-Tyr-Arg, GGYR), which is not transported by di- or tripeptide transporters, was glycosylated with p-(succinylamido)phenyl alpha- or beta-D-glucopyranoside (alpha,beta-SAPG) to investigate whether these glycosylated molecules are transported by the Na+-dependent D-glucose transporter. Their uptake into brush-border membrane vesicles (BBMVs) and transport through the intestinal membrane were examined using the rapid filtration technique and the everted sac method. It was observed that glycosylation at the alpha-amino position of GGYR increased resistance to aminopeptidase activity and inhibited its degradation. When alpha- and beta-SAPG-GGYR were incubated with BBMVs, overshoot uptake was observed about 2 min after the start of incubation in the presence of an inward Na+ gradient. This uptake remained unaffected by the addition of GGYR while it was significantly inhibited when Na+ was replaced with K+ or alpha- and beta-SAPG-GGYR were incubated with BBMVs at 4 degrees C. Uptake was also markedly inhibited either with 1 mM phloridzin or 10 mM D-glucose. These findings suggested that the Na+-dependent glucose transporter (SGLT-1) played an important role in the uptake of both alpha- and beta-SAPG-GGYR into BBMVs. A comparison of alpha- with beta-SAPG-GGYR revealed that the amount of beta-SAPG-GGYR taken up was greater than that of alpha-SAPG-GGYR. From the everted sac method data, it was shown that the elimination clearance from the mucosal side, CLel, and permeation clearance to the serosal side, CLp, were 15.82 +/- 6.83 and 0.83 +/- 0.06 mu l/min/cm for alpha-SAPG-GGYR and 44.52 +/- 3.61 and 3.50 +/- 0.81 mu L/min/cm for beta-SAPG-GGYR, respectively, and that alpha-SAPG-GGYR was more resistant to enzymatic degradation than beta-SAPG-GGYR. Permeation of both alpha- and beta-SAPG-GGYR was inhibited in the presence of D-glucose and in the absence of a Na+ gradient, suggesting that both alpha- and beta-SAPG-GGYR were transported by the Na+-dependent D-glucose transporter. The permeation clearance transported by the Na+-dependent D-glucose transporter, (CLp)(Na+) of beta-SAPG-GGYR was about 5 times greater than that for alpha-SAPG-GGYR. This result may be ascribable to the fact that the beta-form of glucose has higher affinity to SGLT-1 than the alpha-form. The results of the present study encourage further investigations on improvements in intestinal absorption of peptide drugs by glycosylation.

  DOI：

  10.1021/js970269p
• 作为产物：
  描述：

  丁二酸酐 、 4-硝基苯-Β-D-吡喃葡萄糖苷 在 palladium on activated charcoal ammonium formate 作用下， 反应 4.0h， 生成 p-(succinylamido)phenyl β-D-glucopyranoside
  参考文献：
  名称：

  Improvement of Intestinal Absorption of Peptide Drugs by Glycosylation: Transport of Tetrapeptide by the Sodium Ion-Dependent D-Glucose Transporter

  摘要：

  A tetrapeptide (Gly-Gly-Tyr-Arg, GGYR), which is not transported by di- or tripeptide transporters, was glycosylated with p-(succinylamido)phenyl alpha- or beta-D-glucopyranoside (alpha,beta-SAPG) to investigate whether these glycosylated molecules are transported by the Na+-dependent D-glucose transporter. Their uptake into brush-border membrane vesicles (BBMVs) and transport through the intestinal membrane were examined using the rapid filtration technique and the everted sac method. It was observed that glycosylation at the alpha-amino position of GGYR increased resistance to aminopeptidase activity and inhibited its degradation. When alpha- and beta-SAPG-GGYR were incubated with BBMVs, overshoot uptake was observed about 2 min after the start of incubation in the presence of an inward Na+ gradient. This uptake remained unaffected by the addition of GGYR while it was significantly inhibited when Na+ was replaced with K+ or alpha- and beta-SAPG-GGYR were incubated with BBMVs at 4 degrees C. Uptake was also markedly inhibited either with 1 mM phloridzin or 10 mM D-glucose. These findings suggested that the Na+-dependent glucose transporter (SGLT-1) played an important role in the uptake of both alpha- and beta-SAPG-GGYR into BBMVs. A comparison of alpha- with beta-SAPG-GGYR revealed that the amount of beta-SAPG-GGYR taken up was greater than that of alpha-SAPG-GGYR. From the everted sac method data, it was shown that the elimination clearance from the mucosal side, CLel, and permeation clearance to the serosal side, CLp, were 15.82 +/- 6.83 and 0.83 +/- 0.06 mu l/min/cm for alpha-SAPG-GGYR and 44.52 +/- 3.61 and 3.50 +/- 0.81 mu L/min/cm for beta-SAPG-GGYR, respectively, and that alpha-SAPG-GGYR was more resistant to enzymatic degradation than beta-SAPG-GGYR. Permeation of both alpha- and beta-SAPG-GGYR was inhibited in the presence of D-glucose and in the absence of a Na+ gradient, suggesting that both alpha- and beta-SAPG-GGYR were transported by the Na+-dependent D-glucose transporter. The permeation clearance transported by the Na+-dependent D-glucose transporter, (CLp)(Na+) of beta-SAPG-GGYR was about 5 times greater than that for alpha-SAPG-GGYR. This result may be ascribable to the fact that the beta-form of glucose has higher affinity to SGLT-1 than the alpha-form. The results of the present study encourage further investigations on improvements in intestinal absorption of peptide drugs by glycosylation.

  DOI：

  10.1021/js970269p