丙氨酰(2)-脑啡肽酰胺-亮氨酸 | 65189-64-2

• 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
• 中文名称: 丙氨酰(2)-脑啡肽酰胺-亮氨酸
• 英文名称: H-Tyr-D-Ala-Gly-Phe-Leu-NH2
• 英文别名: enkephalinamide-Leu, Ala(2)-；(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide
• CAS: 65189-64-2
• 化学式: C₂₉H₄₀N₆O₆
• 分子量: 568.673
• InChiKey: YPERDMXQKOFCQT-JMBSJVKXSA-N

物化性质

• 熔点：
  130-133 °C
• 沸点：
  1005.6±65.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  206
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  丙氨酰(2)-脑啡肽酰胺-亮氨酸 生成 Hydrogen carbonate[(S)-1-[(R)-1-({[(S)-1-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-2-phenyl-ethylcarbamoyl]-methyl}-carbamoyl)-ethylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-trimethyl-ammonium;
  参考文献：
  名称：

  KAWAI, MASAO;FUKUTA, NORIHITO;ITO, NAOKI;KAGAMI, TAKATOYO;BUTSUGAN, YASUO+, INT. J. PEPTIDE AND PROTEIN RES., 35,(1990) N, C. 452-459

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(tert-butyloxycarbonyl)-L-tyrosyl-D-alanine 在 盐酸 、 sodium hydroxide 、 氨 、 水 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 formamide 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 丙氨酰(2)-脑啡肽酰胺-亮氨酸
  参考文献：
  名称：

  Audigier; Mazarguil; Gout, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 173 - 177

  摘要：

  DOI：

文献信息

• Filippi; Biondi; Filira, Farmaco, Edizione Scientifica, 1983, vol. 38, # 10, p. 713 - 724
  作者：Filippi、Biondi、Filira、Rocchi

  DOI：——

  日期：——
• Effects of Amino Acid Chirality and the Chemical Linker on the Cell Permeation Characteristics of Cyclic Prodrugs of Opioid Peptides
  作者：Bianca M. Liederer、Tarra Fuchs、David Vander Velde、Teruna J. Siahaan、Ronald T. Borchardt

  DOI：10.1021/jm050277f

  日期：2006.2.1

  Previously, our laboratory showed that the oxymethyl-modified coumarinic acid (OMCA) cyclic prodrug of the opioid peptide DADLE ([D-Ala(2),D-Leu(5)]-Enk, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH) exhibited low permeation across both the intestinal mucosa and the blood-brain barrier (BBB). This low cell permeation arose from its strong substrate activity for efflux transporters in these biological barriers. In an attempt to determine whether the chirality of the amino acid asymmetric centers could influence the solution structure of the cyclic prodrugs and thus their substrate activities for efflux transporters, we synthesized cyclic prodrugs of the opioid peptides H-Tyr-Ala-Gly-Phe-D-Leu-OH ([Ala(2),D-Leu(5)]-Enk), H-Tyr-D-Ala-Gly-Phe-Leu-OH ([D-Ala(2),Leu(5)]-Enk), and H-Tyr-Ala-Gly-Phe-Leu-OH ([Ala(2),Leu(5)]-Enk). In an attempt to determine whether the chemical linker (OMCA) bestowed efflux substrate activity on the cyclic prodrugs, we synthesized capped linear derivatives (acetylated on the N-terminal and amidated on the C-terminal end) of [Ala(2),D-Leu(5)]-Enk, [D-Ala(2),Leu(5)]-Enk, and [Ala(2),Leu(5)]-Enk. The solution conformations of the cyclic prodrugs were determined by molecular dynamics simulations using two-dimensional NMR data. The physicochemical properties (molecular surface area, polar surface area, and cLogP) were estimated computationally using Sybyl. Cell permeation characteristics were assessed using Caco-2 cells in the presence and absence of known inhibitors of efflux transporters. Despite apparent differences in their solution conformations and their physicochemical properties, the cyclic prodrugs of DADLE, [Ala(2),D-Leu(5)]-Enk, [D-Ala(2),Leu(5)]-Enk, and [Ala(2),Leu(5)]-Enk all exhibited strong substrate activity for efflux transporters in Caco-2 cells. In contrast, the capped linear derivatives of [Ala(2),D-Leu(5)]-Enk, [D-Ala(2),Leu(5)]-Enk, and [Ala(2),Leu(5)]-Enk exhibited very poor substrate activity for efflux transporters in Caco-2 cells. Therefore, the substrate activities of the cyclic prodrugs for efflux transporters in Caco-2 cells and in the intestinal mucosa and the BBB in vivo are most likely due to the chemical linker used to prepare these molecules and/or its effect on solution structures of the prodrugs.
• KAWAI, MASAO;FUKUTA, NORIHITO;ITO, NAOKI;KAGAMI, TAKATOYO;BUTSUGAN, YASUO+, INT. J. PEPTIDE AND PROTEIN RES., 35,(1990) N, C. 452-459
  作者：KAWAI, MASAO、FUKUTA, NORIHITO、ITO, NAOKI、KAGAMI, TAKATOYO、BUTSUGAN, YASUO+

  DOI：——

  日期：——
• Kojro, Elzbieta; Grzonka, Zbigniew, Polish Journal of Chemistry, 1984, vol. 58, # 1-3, p. 163 - 171
  作者：Kojro, Elzbieta、Grzonka, Zbigniew

  DOI：——

  日期：——
• Kundu, Bijoy; Agarwal, Kamlesh C., Journal of Chemical Research, Synopses, 1996, # 4, p. 200 - 201
  作者：Kundu, Bijoy、Agarwal, Kamlesh C.

  DOI：——

  日期：——