N-succinimidyl-D-valine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-succinimidyl-D-valine
• 英文别名: N-succinyl-d-valine；(2R)-2-(2,5-dioxopyrrolidin-1-yl)-3-methylbutanoic acid
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: JDYJYXLXWZCRFG-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-succinimidyl-D-valine 、 荧光素5-马来酰亚胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以38.8%的产率得到
  参考文献：
  名称：

  Fluorogenic approach to evaluating prodrug hydrolysis and stability in live cells

  摘要：

  Fluorescein diester which is conjugated with cell membrane permeable Arg9 peptide was proposed as probe for ester prodrug stability and drug release study in living cells. a-Amino protected D-Val and L-Ala which bear differently hindered side chains were used to afford model diesters of 5-maleimide-fluorescein. Such fluorescein diesters were further conjugated with a Cys containing cell membrane permeable Arg9 peptide via thiol-ene crosslink reaction. The resulted conjugates of fluorescein diester and Arg9 peptide were purified with HPLC and characterized with MALDI-TOF MS. Upon incubation with cultured cells, the fluorescein diesters were delivered into the cells, the following hydrolysis of fluorescein diesters and release of fluorescein inside living cells were observed by monitoring the fluorescence accumulation. Fluorescence microscopic imaging studies of HeLa cells treated with fluorescein L-Ala diester show strong fluorescence accumulation in 30 min indicating fast hydrolysis of fluorescein diester and fluorescein release; in contrast D-Val diester remains stable inside cells evidenced by margin fluorescence formation. Further flowcytometry studies on the fluorescein diester-Arg9 conjugate treated cells show that the hydrolysis t1/2 for L-Ala diester is 15 min. The results also show that Arg9 peptide not only transports the ester probes into cell efficiently but also can retain and concentrate hydrolytic product fluorescein inside cells so that the accumulated fluorescence can be accurately quantified. This fluorogenic probe approach provides feasible applications in dynamic studies on ester prodrug hydrolysis and release, facilitating screening and optimization of prodrug structures in living cell settings.

  DOI：

  10.1016/j.bmc.2019.01.030
• 作为产物：
  描述：

  丁二酸酐 、 D-缬氨酸 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以86.5%的产率得到N-succinimidyl-D-valine
  参考文献：
  名称：

  Fluorogenic approach to evaluating prodrug hydrolysis and stability in live cells

  摘要：

  Fluorescein diester which is conjugated with cell membrane permeable Arg9 peptide was proposed as probe for ester prodrug stability and drug release study in living cells. a-Amino protected D-Val and L-Ala which bear differently hindered side chains were used to afford model diesters of 5-maleimide-fluorescein. Such fluorescein diesters were further conjugated with a Cys containing cell membrane permeable Arg9 peptide via thiol-ene crosslink reaction. The resulted conjugates of fluorescein diester and Arg9 peptide were purified with HPLC and characterized with MALDI-TOF MS. Upon incubation with cultured cells, the fluorescein diesters were delivered into the cells, the following hydrolysis of fluorescein diesters and release of fluorescein inside living cells were observed by monitoring the fluorescence accumulation. Fluorescence microscopic imaging studies of HeLa cells treated with fluorescein L-Ala diester show strong fluorescence accumulation in 30 min indicating fast hydrolysis of fluorescein diester and fluorescein release; in contrast D-Val diester remains stable inside cells evidenced by margin fluorescence formation. Further flowcytometry studies on the fluorescein diester-Arg9 conjugate treated cells show that the hydrolysis t1/2 for L-Ala diester is 15 min. The results also show that Arg9 peptide not only transports the ester probes into cell efficiently but also can retain and concentrate hydrolytic product fluorescein inside cells so that the accumulated fluorescence can be accurately quantified. This fluorogenic probe approach provides feasible applications in dynamic studies on ester prodrug hydrolysis and release, facilitating screening and optimization of prodrug structures in living cell settings.

  DOI：

  10.1016/j.bmc.2019.01.030