nipecotyl-N-MePhe-N-MePhe-N-MePhe-N-MePhe-CONH₂ | 1215027-82-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: nipecotyl-N-MePhe-N-MePhe-N-MePhe-N-MePhe-CONH₂
• 英文别名: NIP-N-MePhe-N-MePhe-N-MePhe-N-MePhe-CONH₂；N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]-N-methylpiperidine-3-carboxamide
• CAS: 1215027-82-9
• 化学式: C₄₆H₅₆N₆O₅
• 分子量: 772.988
• InChiKey: RHDVLLJJSIYHGH-MPLVUSNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  57
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-硝基苯磺酸甲酯 、 Fmoc-L-苯丙氨酸 、 N-(9-芴甲氧羰酰基)-N-甲基-L-苯丙氨酸 、 (±)-N-Fmoc-3-哌啶甲酸 Fmoc-DL-哌啶甲酸 在 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 以90%的产率得到nipecotyl-N-MePhe-N-MePhe-N-MePhe-N-MePhe-CONH₂
  参考文献：
  名称：

  N-Methyl Phenylalanine-Rich Peptides as Highly Versatile Blood−Brain Barrier Shuttles

  摘要：

  Here we studied the capacity of N-MePhe-(N-MePhe)(3)-CONH2, Cha-(N-MePhe)(3)-CONH2, and 2Nal-(N-MePhe)(3)-CONH2 to carry various drugs (cargos) in in vitro blood brain barrier (BBB) models in order to determine the versatility of these peptides as BBB-shuttles for drug delivery to the brain. Using SPPS, the peptides were coupled to GABA, Nip, and ALA to examine their passive BBB permeation by means of PAMPA and their lipophilicity by IAMC. Unaided, these nonpermeating drugs alone did not cross the PAMPA barrier and the BBB passively; however, the peptides tested as potential BBB shuttles transferred them by passive transfer through the PAMPA phospholipid. The permeability of peptides that showed the highest permeability in PAMPA, and Ac-N-MePhe-(N-MePhe)(3)-CONH2 as the parent peptide was also examined in bovine brain microvessel endothelial cells (BBMECs). These peptide-based BBB shuttles open up the possibility to overcome the formidable obstacle of the BBB, thereby achieving drug delivery to the brain.

  DOI：

  10.1021/jm901654x

文献信息

• ‘À la Carte’ Peptide Shuttles: Tools to Increase Their Passage across the Blood-Brain Barrier
  作者：Morteza Malakoutikhah、Bernat Guixer、Pol Arranz-Gibert、Meritxell Teixidó、Ernest Giralt

  DOI：10.1002/cmdc.201300575

  日期：2014.7

  In several cases, we assessed the BBB permeability of both the shuttles alone and linked to a few cargos. Our results show how factors such as stereochemistry or halogen content influences the passage across the BBB and, more importantly, opens the way to a strategy of peptide shuttles ‘à la carte′, in which a particular fine‐tuned shuttle is used for each specific cargo.

  有效地将药物输送到大脑的非侵入性方法是未满足的需求。进入大脑的分子受到大脑血管内皮细胞建立的血脑屏障（BBB）的调节。被动扩散是有机化合物用来穿过这些内皮细胞的主要机制之一。穿过血脑屏障的通道主要由分子的某些物理化学性质（如亲脂性，大小以及氢键供体和受体的存在）决定。促进有机化合物穿过血脑屏障的一种新兴策略是使用肽穿梭。1个在使用这种方法时，很明显，BBB前方的渗透率是由货物和航天飞机的综合理化特性决定的。本文中，我们报告了一种更有效的肽穿梭序列（N- MePhe）n的一系列变体的合成。其中包括多种结构特征，例如各种骨架立体化学或存在非天然氨基酸（包括卤化残基）。在某些情况下，我们评估了两个航天飞机本身以及与少量货物相关联的BBB渗透性。我们的结果表明，诸如立体化学或卤素含量之类的因素如何影响穿过BBB的通道，更重要的是，为肽穿梭点菜策略打下了基础，在这种策略中，每种特定的蛋白都使用了特定的微调穿梭剂货物。
• <i>N</i>-Methyl Phenylalanine-Rich Peptides as Highly Versatile Blood−Brain Barrier Shuttles
  作者：Morteza Malakoutikhah、Roger Prades、Meritxell Teixidó、Ernest Giralt

  DOI：10.1021/jm901654x

  日期：2010.3.25

  Here we studied the capacity of N-MePhe-(N-MePhe)(3)-CONH2, Cha-(N-MePhe)(3)-CONH2, and 2Nal-(N-MePhe)(3)-CONH2 to carry various drugs (cargos) in in vitro blood brain barrier (BBB) models in order to determine the versatility of these peptides as BBB-shuttles for drug delivery to the brain. Using SPPS, the peptides were coupled to GABA, Nip, and ALA to examine their passive BBB permeation by means of PAMPA and their lipophilicity by IAMC. Unaided, these nonpermeating drugs alone did not cross the PAMPA barrier and the BBB passively; however, the peptides tested as potential BBB shuttles transferred them by passive transfer through the PAMPA phospholipid. The permeability of peptides that showed the highest permeability in PAMPA, and Ac-N-MePhe-(N-MePhe)(3)-CONH2 as the parent peptide was also examined in bovine brain microvessel endothelial cells (BBMECs). These peptide-based BBB shuttles open up the possibility to overcome the formidable obstacle of the BBB, thereby achieving drug delivery to the brain.