penetratin | 214556-79-3

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: penetratin
• 英文别名: RQIKIWFQNRRMKWKK-NH₂；RQIKIWFQNRRMKWKK；(2S)-N-[(2S,3S)-1-[(2S)-6-amino-1-[(2S,3S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-6-amino-1-[(2S)-1-[(2S)-6-amino-1-[(2S)-6-amino-1-hydroxy-1-iminohexan-2-yl]imino-1-hydroxyhexan-2-yl]imino-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]imino-1-hydroxyhexan-2-yl]imino-1-hydroxy-4-methylsulfanylbutan-2-yl]imino-5-carbamimidamido-1-hydroxypentan-2-yl]imino-5-carbamimidamido-1-hydroxypentan-2-yl]imino-1,4-dihydroxy-4-iminobutan-2-yl]imino-1,5-dihydroxy-5-iminopentan-2-yl]imino-1-hydroxy-3-phenylpropan-2-yl]imino-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]imino-1-hydroxy-3-methylpentan-2-yl]imino-1-hydroxyhexan-2-yl]imino-1-hydroxy-3-methylpentan-2-yl]-2-[[(2S)-2-amino-5-carbamimidamido-1-hydroxypentylidene]amino]pentanediimidic acid
• CAS: 214556-79-3
• 化学式: C₁₀₄H₁₆₉N₃₅O₁₉S
• 分子量: 2245.77
• InChiKey: MCYTYTUNNNZWOK-LCLOTLQISA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  159
• 可旋转键数：
  83
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  982
• 氢给体数：
  35
• 氢受体数：
  28

制备方法与用途

肽类似物

穿膜肽 (CPPs) 是一类由10至30个氨基酸组成的短肽。这类多肽最初因其能介导蛋白质在细胞内的传递而被发现，并因具有卓越的跨细胞膜能力而在药物递送领域得到广泛应用。这些多肽通常含有大量正电荷，能够与siRNA和反义寡核苷酸（ASO）富含负电荷的磷酸骨架形成离子聚集体。因此，CPPs 通常用于携带中性骨架的磷酰二胺-吗啉代寡核苷酸 (PMO) 和肽核酸 (PNA)。

阳离子型穿膜肽

阳离子型穿膜肽由富含碱性氨基酸（在中性pH下具有净正电荷）如精氨酸（R）、赖氨酸（K）和组氨酸（H）的短肽组成。常见的例子包括TAT、Penetratin、Polyarginine、P22N、DPV3 和 DPV6 等。其中，精氨酸含有胍基，这种碱性的、易水解的化学基团能与细胞膜上带负电荷的磷酸基团形成氢键，在生理pH值条件下促进穿膜肽入膜。

研究表明，寡聚精氨酸（从3 R到12 R）的研究表明，当精氨酸的数量至少为8个时才具有穿膜能力，并且随着精氨酸数量增加，穿膜能力逐渐增强。相比之下，赖氨酸虽然也带有正电荷，但不含胍基，因此单独存在时其穿膜效率较低。Futaki等人（2001）发现，阳离子型细胞穿膜肽至少含有8个带正电荷的氨基酸才能达到良好的穿膜效果。

尽管带正电荷的氨基酸残基对于穿膜肽穿膜至关重要，但其他氨基酸也同样重要。例如，在Penetratin中，当第14位精氨酸突变为脯氨酸（W14突变成F）后，其穿膜性就消失了。

反应信息

• 作为产物：
  描述：

  Fmoc-L-色氨酸 、 Fmoc-L-谷氨酰胺 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-蛋氨酸 、 Fmoc-L-异亮氨酸 、 FMOC-赖氨酸 、 Fmoc-L-天冬酰胺 、 FMOC-L-精氨酸 、 (2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[(4-phenylphenyl)methoxy]oxane-2-carboxylic acid 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 、 哌啶 作用下， 反应 0.22h， 生成 penetratin
  参考文献：
  名称：

  Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells

  摘要：

  The in vivo utility of technologies employing cell penetrating peptides and bioportides may be compromised by the general capacity of polycationic peptides to activate mast cell secretion. Moreover, the same technologies could be exploited in a clinical setting either to directly modulate intrinsic exocytotic mechanisms or to load mast cells with bioactive cargoes. Comparative investigations identified two cell penetrating vectors, Tat and C105Y, which readily translocate into mast cells without inducing receptor-independent exocytosis. Efficient Tat transduction also enabled the intracellular delivery and accumulation of cargoes within discrete intracellular compartments. A tetramethylrhodamine-Tat conjugate is effectively translocated into the secretory lysosomes of RBL-2H3 cells. In contract, the intracellular delivery of avidin, as a non-covalent complex with a biotinylated Tat vector, is also efficient but the protein is predominantly accumulated outside of secretory lysosomes. Significantly, both cargoes can be subsequently released following mast cell stimulation either by mastoparan, a wasp venom secretagogue, or by the physiological mechanism of antigen-induced aggregation of high affinity IgE receptors. These studies indicate that mast cells could be exploited to direct the delivery of bioactive agents to disease sites as an innovative cell-mediated therapy. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2015.02.005

文献信息

• Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells
  作者：John Howl、Sarah Jones

  DOI：10.1016/j.jconrel.2015.02.005

  日期：2015.3

  The in vivo utility of technologies employing cell penetrating peptides and bioportides may be compromised by the general capacity of polycationic peptides to activate mast cell secretion. Moreover, the same technologies could be exploited in a clinical setting either to directly modulate intrinsic exocytotic mechanisms or to load mast cells with bioactive cargoes. Comparative investigations identified two cell penetrating vectors, Tat and C105Y, which readily translocate into mast cells without inducing receptor-independent exocytosis. Efficient Tat transduction also enabled the intracellular delivery and accumulation of cargoes within discrete intracellular compartments. A tetramethylrhodamine-Tat conjugate is effectively translocated into the secretory lysosomes of RBL-2H3 cells. In contract, the intracellular delivery of avidin, as a non-covalent complex with a biotinylated Tat vector, is also efficient but the protein is predominantly accumulated outside of secretory lysosomes. Significantly, both cargoes can be subsequently released following mast cell stimulation either by mastoparan, a wasp venom secretagogue, or by the physiological mechanism of antigen-induced aggregation of high affinity IgE receptors. These studies indicate that mast cells could be exploited to direct the delivery of bioactive agents to disease sites as an innovative cell-mediated therapy. (C) 2015 Elsevier B.V. All rights reserved.