N1-benzyloxycarbonyl-N8-(Nα-t-butoxycarbonyl-Ng-tosylarginyl-Nα-methyl-Ng-tosylarginyl-D-leucyl)-1,8-octanediamine | 205874-67-5

• 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: N1-benzyloxycarbonyl-N8-(Nα-t-butoxycarbonyl-Ng-tosylarginyl-Nα-methyl-Ng-tosylarginyl-D-leucyl)-1,8-octanediamine
• 英文别名: N¹-benzyloxycarbonyl-N⁸-(N^α-t-butoxycarbonyl-N^g-tosylarginyl-N^α-methyl-N^g-tosylarginyl-D-leucyl)-1,8-octanediamine；N¹-benzyloxycarbonyl-N⁸-(N^α-t-butoxycarbonyl-N^g-tosylarginyl-N^g-tosyl-N^α-methylarginyl-D-leucyl)-1,8-octanediamine
• CAS: 205874-67-5
• 化学式: C₅₄H₈₃N₁₁O₁₁S₂
• 分子量: 1126.45
• InChiKey: BFCVUYSTDJQHMK-VANFPJICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  78.0
• 可旋转键数：
  31.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  319.27
• 氢给体数：
  10.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  N1-benzyloxycarbonyl-N8-(Nα-t-butoxycarbonyl-Ng-tosylarginyl-Nα-methyl-Ng-tosylarginyl-D-leucyl)-1,8-octanediamine 在 钯 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis

  摘要：

  The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH-NBD) for the purpose of quantification, The degradation half-life of 001-C8-NBD in jejunal homogenate (1 mg/mL) was 99.5 min, which was significantly longer than that of natural leucine enkephalin (1.14 min). The absorption of 001-C8-NBD was evaluated by the vascular-perfusion method. Intact 001-C8-NBD appeared in the blood time-dependently and the absorption volume at 30 min (2.75 +/- 0.14 mu L/cm intestine) was significantly larger than that of [H-3]PEG 900 (0.88 +/- 0.13 mu L/cm intestine), of which membrane permeability is very low. The absorption of 001-C8-NBD was greatly reduced by an adsorptive-mediated endocytosis inhibitor, protamine (10 mM). No inhibition of the absorption of [H-3]PEG 900 by protamine was observed. The intestinal absorption was also measured by an in vivo loop method. The absorption clearance of 001-C8-NBD measured by this method (0.083 +/- 0.008 mu L/min/cm intestine) was comparable to that obtained by the vascular perfusion method (0.092 +/- 0.005 mu L/min/cm intestine). All of these data suggested that 001-C8-NBD was absorbed as the intact oligopeptide in the intestine in vivo. Adsorptive-mediated transcytosis is suggested to have enormous potential as an oral delivery system for peptide and/or protein drugs. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00031-5
• 作为产物：
  描述：

  BOC-D-亮氨酸 在 TEA 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.83h， 生成 N1-benzyloxycarbonyl-N8-(Nα-t-butoxycarbonyl-Ng-tosylarginyl-Nα-methyl-Ng-tosylarginyl-D-leucyl)-1,8-octanediamine
  参考文献：
  名称：

  Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis

  摘要：

  The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH-NBD) for the purpose of quantification, The degradation half-life of 001-C8-NBD in jejunal homogenate (1 mg/mL) was 99.5 min, which was significantly longer than that of natural leucine enkephalin (1.14 min). The absorption of 001-C8-NBD was evaluated by the vascular-perfusion method. Intact 001-C8-NBD appeared in the blood time-dependently and the absorption volume at 30 min (2.75 +/- 0.14 mu L/cm intestine) was significantly larger than that of [H-3]PEG 900 (0.88 +/- 0.13 mu L/cm intestine), of which membrane permeability is very low. The absorption of 001-C8-NBD was greatly reduced by an adsorptive-mediated endocytosis inhibitor, protamine (10 mM). No inhibition of the absorption of [H-3]PEG 900 by protamine was observed. The intestinal absorption was also measured by an in vivo loop method. The absorption clearance of 001-C8-NBD measured by this method (0.083 +/- 0.008 mu L/min/cm intestine) was comparable to that obtained by the vascular perfusion method (0.092 +/- 0.005 mu L/min/cm intestine). All of these data suggested that 001-C8-NBD was absorbed as the intact oligopeptide in the intestine in vivo. Adsorptive-mediated transcytosis is suggested to have enormous potential as an oral delivery system for peptide and/or protein drugs. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00031-5

文献信息

• Design and Synthesis of Peptides Passing through the Blood-Brain Barrier
  作者：Tateaki Wakamiya、Makoto Kamata、Shoichi Kusumoto、Hiroyuki Kobayashi、Yoshimichi Sai、Ikumi Tamai、Akira Tsuji

  DOI：10.1246/bcsj.71.699

  日期：1998.3

  The blood-brain barrier (BBB) is a highly selective membranous barrier regulating the transport of substances in blood into the brain parenchyma. At present, delivery of biologically active peptides or peptide drugs into the brain is quite an important subject from the standpoint of chemotherapy for brain diseases. H–MeTyr–Arg–MeArg–d-Leu–NH(CH2)8NH2 termed 001-C8 was first synthesized to elucidate the structural specificity of peptides for passing through the BBB. The Nα-methylamino acid and d-amino acid residues were appropriately situated in this peptide to protect against the digestion by peptidase. Furthermore, a number of basic peptides were prepared as 001-C8 analogs for studying the relationship between structure and BBB permeability of peptides.

  血脑屏障（BBB）是一种高度选择性的膜屏障，调控血液中的物质向脑实质内的转运。目前，从脑部疾病化学治疗的角度出发，如何将生物活性肽或肽类药物递送入脑是一个相当重要的课题。首先合成了名为001-C8的H-MeTyr-Arg-MeArg-d-Leu-NH(CH2)8NH2，以阐明肽穿越BBB所需的结构特异性。在此肽中，Nα-甲基氨基酸和d-氨基酸残基适当地分布，以防止被肽酶降解。此外，还制备了一批001-C8类似物，即多种碱性肽，用于研究肽的结构与其BBB通透性之间的关系。