N-6-aminohexyl-amphoterin B | 432546-41-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-6-aminohexyl-amphoterin B
• CAS: 432546-41-3
• 化学式: C₅₃H₈₆N₂O₁₇
• 分子量: 1023.27
• InChiKey: LWPUYESDFCVLHW-QMXVZLFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  72.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  331.64
• 氢给体数：
  13.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  双琥珀酰亚胺辛二酸酯 、 N-6-aminohexyl-amphoterin B 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以22%的产率得到(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-[6-[[8-[6-[[(2R,3S,4S,5S,6R)-2-[[(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-36-carboxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaen-33-yl]oxy]-3,5-dihydroxy-6-methyloxan-4-yl]amino]hexylamino]-8-oxooctanoyl]amino]hexylamino]-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
  参考文献：
  名称：

  Amphotericin B Covalent Dimers Forming Sterol-Dependent Ion-Permeable Membrane Channels

  摘要：

  Polyenemacrolides such as amphotericin B (AmB) were thought to assemble together and form an ion channel across plasma membranes. Their antimicrobial activity has been accounted for by this assemblage, whose stability and activity are dependent on sterol constituents of lipid bilayer membranes. The structure of this channel-like assemblage formed in biomembranes has been a target of extensive investigations for a long time. For the first step to this goal, we prepared several AmB dimers with various linkers and tested for their channel-forming activity. Among these, AmB dimers that bore an aminoalkyl-dicarboxylate tether covalently linked between amino groups of AmB showed potent hemolytic activity. Furthermore, K+ influx actions monitored by measuring the pH of the liposome lumen by 31P NMR revealed that the dimers formed the molecular assemblage similar to that of AmB in phospholipid membrane. Judging from changes in 31P NMR spectra, the dimers appeared to induce "all-or-none"-type ion flux across the liposome membrane in the presence of ergosterol, which suggested that the ion channel formed by ergosterol/dimer is similar to that of AmB. With these data in hand, we are now trying to elucidate the structure of the ion-channel complex by making the labeled conjugates of AmB for NMR measurements.

  DOI：

  10.1021/ja012026b
• 作为产物：
  描述：

  两性霉素B 在 哌啶 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 34.0h， 生成 N-6-aminohexyl-amphoterin B
  参考文献：
  名称：

  Amphotericin B Covalent Dimers Forming Sterol-Dependent Ion-Permeable Membrane Channels

  摘要：

  Polyenemacrolides such as amphotericin B (AmB) were thought to assemble together and form an ion channel across plasma membranes. Their antimicrobial activity has been accounted for by this assemblage, whose stability and activity are dependent on sterol constituents of lipid bilayer membranes. The structure of this channel-like assemblage formed in biomembranes has been a target of extensive investigations for a long time. For the first step to this goal, we prepared several AmB dimers with various linkers and tested for their channel-forming activity. Among these, AmB dimers that bore an aminoalkyl-dicarboxylate tether covalently linked between amino groups of AmB showed potent hemolytic activity. Furthermore, K+ influx actions monitored by measuring the pH of the liposome lumen by 31P NMR revealed that the dimers formed the molecular assemblage similar to that of AmB in phospholipid membrane. Judging from changes in 31P NMR spectra, the dimers appeared to induce "all-or-none"-type ion flux across the liposome membrane in the presence of ergosterol, which suggested that the ion channel formed by ergosterol/dimer is similar to that of AmB. With these data in hand, we are now trying to elucidate the structure of the ion-channel complex by making the labeled conjugates of AmB for NMR measurements.

  DOI：

  10.1021/ja012026b