1,5-dihexadecyl N-glutamyl-L-glutamate | 299918-36-8

• 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: 1,5-dihexadecyl N-glutamyl-L-glutamate
• 英文别名: 1,5-Dihexadecyl n-glutamyl-l-glutamate；(4S)-4-amino-5-[[(2S)-1,5-dihexadecoxy-1,5-dioxopentan-2-yl]amino]-5-oxopentanoic acid
• CAS: 299918-36-8
• 化学式: C₄₂H₈₀N₂O₇
• 分子量: 725.106
• InChiKey: XTHAXJQOVBOUHZ-UWXQCODUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.9
• 重原子数：
  51
• 可旋转键数：
  41
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  dihexadecyl ((S)-5-(tert-butoxy)-2-((tert-butoxycarbonyl)amino)-5-oxopentanoyl)-L-glutamate 在 三氟乙酸 作用下， 生成 1,5-dihexadecyl N-glutamyl-L-glutamate
  参考文献：
  名称：

  Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo

  摘要：

  We developed pH-responsive liposomes containing synthetic glutamic acid-based zwitterionic lipids and evaluated their properties both in vitro and in vivo with the aim of constructing an efficient liposome-based systemic drug delivery system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized as a pH-responsive component of liposomes that respond to endosomal pH. The zeta potential of liposomes containing L1 or L2 was positive when the solution pH was below 4.6 or 5.6, respectively, but negative at higher pH values. The pH-responsive liposomes showed improved fusogenic potential to an endosome-mimicking anionic membrane at acidic pH, where the zeta potential of the liposomes was positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing L1 or 12, and clarified by confocal microscopic studies that the contents were rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a drug delivery system. Intravenously injected L2-liposomes displayed blood persistence comparable to that of conventional phospholipid (PC)-based liposomes. Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based liposomes against a xenograft breast cancer tumor in vivo. Thus, the high performance of L2-liposomes results from both efficient intracellular drug delivery and comparable blood persistence in comparison with the conventional PC-based liposomes in vitro and in vivo. (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2009.10.023

文献信息

• AMPHOTERIC LIPID COMPOUND AND USE THEREOF
  申请人：JCR Pharmaceuticals Co., Ltd.

  公开号：EP1420010B1

  公开（公告）日：2011-03-16
• AMPHIPATHIC MOLECULE, MOLECULAR AGGREGATE COMPRISING THE AMPHIPATHIC MOLECULE, AND USE OF THE MOLECULAR AGGREGATE
  申请人：Waseda University

  公开号：EP2157096B1

  公开（公告）日：2013-02-20
• AMPHIPHILIC MOLECULE, MOLECULAR ASSEMBLY COMPRISING THE AMPHIPHILIC MOLECULE, AND USE OF THE MOLECULAR ASSEMBLY
  申请人：Takeoka Shinji

  公开号：US20100209458A1

  公开（公告）日：2010-08-19

  The present invention provides an amphiphilic molecule having a plurality of zwitterionic functional groups in its hydrophilic moiety and a molecular assembly comprising the amphiphilic molecule as a constituent lipid. According to a preferred embodiment of the present invention, the molecular assembly of the present invention forms a stable vesicular structure under a physiological pH environment to carry a substance of interest in the vesicular structure, and can release the substance of interest to the outside of the vesicular structure when it is deformed under an acidic pH environment. The molecular assembly of the present invention can be used as a carrier for a drug, a probe, a nucleic acid, a protein or the like.
• US8241647B2
  申请人：——

  公开号：US8241647B2

  公开（公告）日：2012-08-14
• Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo
  作者：Yosuke Obata、Shoji Tajima、Shinji Takeoka

  DOI：10.1016/j.jconrel.2009.10.023

  日期：2010.3

  We developed pH-responsive liposomes containing synthetic glutamic acid-based zwitterionic lipids and evaluated their properties both in vitro and in vivo with the aim of constructing an efficient liposome-based systemic drug delivery system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized as a pH-responsive component of liposomes that respond to endosomal pH. The zeta potential of liposomes containing L1 or L2 was positive when the solution pH was below 4.6 or 5.6, respectively, but negative at higher pH values. The pH-responsive liposomes showed improved fusogenic potential to an endosome-mimicking anionic membrane at acidic pH, where the zeta potential of the liposomes was positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing L1 or 12, and clarified by confocal microscopic studies that the contents were rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a drug delivery system. Intravenously injected L2-liposomes displayed blood persistence comparable to that of conventional phospholipid (PC)-based liposomes. Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based liposomes against a xenograft breast cancer tumor in vivo. Thus, the high performance of L2-liposomes results from both efficient intracellular drug delivery and comparable blood persistence in comparison with the conventional PC-based liposomes in vitro and in vivo. (C) 2009 Elsevier B.V. All rights reserved.