| 236404-48-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• CAS: 236404-48-1
• 化学式: C₄₀H₅₀N₂O₈
• 分子量: 686.846
• InChiKey: MASNDTVNBIIWED-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.79
• 重原子数：
  50.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  120.47
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 11.0h， 以72%的产率得到(S)-10-(2-tert-butoxy-2-oxoethyl)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-2,13-dioxa-4,10-diaza pentadecane-5-carboxylic acid
  参考文献：
  名称：

  Single- or Dual-Mode Switching of Semisynthetic Ribonuclease S′ with an Iminodiacetic Acid Moiety in Response to the Copper(II) Concentration

  摘要：

  Ribonuclease S' bearing iminodiacetic acid as a metal-binding site was designed and semisynthesized by self-assembly of native S-protein with chemically modified S-peptide. Iminodiacetic acid-appended amino acid (Ida(4)) was synthesized and incorporated into the S-peptide sequence by solid-phase peptide synthesis based on Fmoc chemistry at a single site or double sites of the solvent-exposed side of the S-peptide. Circular dichroism (CD) spectroscopy of these S-peptides confirmed that the Cu-II ion induced an increase or decrease of alpha-helix conformation depending on the replacement position. S-Peptide/S-protein titration monitored by conventional enzymatic activity and UV or CD spectroscopy demonstrated that various S-peptides form a stable complex (Ida(4)-RNase S') with S-protein, except when Met13 and Asp14 are replaced with Ida4. In Cu-II titration and thermal denaturation experiments with single-site replacement mutants, Cu-II binding occurred at 1:1 stoichiometry of Ida(4)/Cu-II with perturbation of the a-helix conformation. Both 2:1 and 2:2 stoichiometries were achieved by addition of Cu-II ions to double-site mutants, and were dependent on the Cu-II concentration. Most importantly, the A6/E9Ida(4)-RNase S' mutant shows cooperative binding of Cu-II ion with two Ida(4); holoenzyme stability is enhanced at 2:1 stoichiometry, but at 2:2 stoichiometry, two Ida(4) sites independently bind two Cu-II ions, and the mutant is destabilized. Other double mutants showed simple destabilization of 3D structure upon Cu-II binding. The response of the enzymatic activity of these Ida4-RNase S' to the concentration of Cu-II ion was evaluated by the hydrolysis of polyuridiric acid catalyzed by RNaseS' mutants. The Cu-II-induced activity change of single and double mutants agreed well with the structural response to Cu-II, that is, the activity of AG/E9Ida(4)-RNaseS' was enhanced upon cooperative Cu-II binding at 2:1 stoichiometry and then suppressed at the 2:2 ratio. The activity of all other mutants was simply suppressed by Cu-II ions. These results represent successful switching of A6/E9Ida(4)-RNase S' activity in dual mode, that is, suppression (OFF) or enhancement (ON), depending on the environmental Cu-II concentration. Thus it has been established that rational design of a metal-binding site can confer the dual mode of response to a metal cation on the structure and activity of an enzyme.

  DOI：

  10.1002/(sici)1521-3765(19990503)5:5<1503::aid-chem1503>3.0.co;2-6
• 作为产物：
  描述：

  Fmoc-Lys(Boc)-OBn 在 碳酸氢钠 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 105.0h， 生成
  参考文献：
  名称：

  Single- or Dual-Mode Switching of Semisynthetic Ribonuclease S′ with an Iminodiacetic Acid Moiety in Response to the Copper(II) Concentration

  摘要：

  Ribonuclease S' bearing iminodiacetic acid as a metal-binding site was designed and semisynthesized by self-assembly of native S-protein with chemically modified S-peptide. Iminodiacetic acid-appended amino acid (Ida(4)) was synthesized and incorporated into the S-peptide sequence by solid-phase peptide synthesis based on Fmoc chemistry at a single site or double sites of the solvent-exposed side of the S-peptide. Circular dichroism (CD) spectroscopy of these S-peptides confirmed that the Cu-II ion induced an increase or decrease of alpha-helix conformation depending on the replacement position. S-Peptide/S-protein titration monitored by conventional enzymatic activity and UV or CD spectroscopy demonstrated that various S-peptides form a stable complex (Ida(4)-RNase S') with S-protein, except when Met13 and Asp14 are replaced with Ida4. In Cu-II titration and thermal denaturation experiments with single-site replacement mutants, Cu-II binding occurred at 1:1 stoichiometry of Ida(4)/Cu-II with perturbation of the a-helix conformation. Both 2:1 and 2:2 stoichiometries were achieved by addition of Cu-II ions to double-site mutants, and were dependent on the Cu-II concentration. Most importantly, the A6/E9Ida(4)-RNase S' mutant shows cooperative binding of Cu-II ion with two Ida(4); holoenzyme stability is enhanced at 2:1 stoichiometry, but at 2:2 stoichiometry, two Ida(4) sites independently bind two Cu-II ions, and the mutant is destabilized. Other double mutants showed simple destabilization of 3D structure upon Cu-II binding. The response of the enzymatic activity of these Ida4-RNase S' to the concentration of Cu-II ion was evaluated by the hydrolysis of polyuridiric acid catalyzed by RNaseS' mutants. The Cu-II-induced activity change of single and double mutants agreed well with the structural response to Cu-II, that is, the activity of AG/E9Ida(4)-RNaseS' was enhanced upon cooperative Cu-II binding at 2:1 stoichiometry and then suppressed at the 2:2 ratio. The activity of all other mutants was simply suppressed by Cu-II ions. These results represent successful switching of A6/E9Ida(4)-RNase S' activity in dual mode, that is, suppression (OFF) or enhancement (ON), depending on the environmental Cu-II concentration. Thus it has been established that rational design of a metal-binding site can confer the dual mode of response to a metal cation on the structure and activity of an enzyme.

  DOI：

  10.1002/(sici)1521-3765(19990503)5:5<1503::aid-chem1503>3.0.co;2-6