YGRKKRRQRRRC-NH₂ | 697226-53-2

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: YGRKKRRQRRRC-NH₂
• 英文别名: YGRKKRRQRRRC-NH2；(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide
• CAS: 697226-53-2
• 化学式: C₆₇H₁₂₄N₃₄O₁₄S
• 分子量: 1662.01
• InChiKey: DLTIMGFUZUCMCF-AIFXSXIMSA-N

物化性质

• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -12.2
• 重原子数：
  116
• 可旋转键数：
  61
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  892
• 氢给体数：
  30
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  YGRKKRRQRRRC-NH₂ 、 丁二酰氯 以 aq. phosphate buffer 为溶剂， 反应 24.0h， 以81%的产率得到
  参考文献：
  名称：

  Acid-Active Cell-Penetrating Peptides for in Vivo Tumor-Targeted Drug Delivery

  摘要：

  Cell-penetrating peptides (CPPs) such as transactivator of transcription (TAT) peptide have long been explored for promoting in vitro cell penetration and nuclear targeting of various cargos, but their positive charges cause strong nonspecific interactions, making them inapplicable for many in vivo applications. In this work, we used TAT to demonstrate a molecular modification approach for inhibiting nonspecific interactions of CPPs in the bloodstream while reactivating their functions in the targeted tissues or cells. The TAT lysine residues' amines were amidized to succinyl amides ((a)TAT), completely inhibiting TAT's nonspecific interactions in the blood compartment; once in the acidic tumor interstitium or internalized into cell endo/lysosomes, the succinyl amides in the (a)TAT were quickly hydrolyzed, fully restoring TAT's functions. Thus, (a)TAT-functionalized poly(ethylene glycol)-block-poly(epsilon-caprolactone) micelles achieved long circulation in the blood compartment and efficiently accumulated and delivered doxorubicin to tumor tissues, giving rise to high antitumor activity and low cardiotoxicity. This amidization strategy effectively and easily enables in vivo applications of CPPs.

  DOI：

  10.1021/ja311180x
• 作为产物：
  描述：

  BOC-甘氨酸 、 Boc-L-谷氨酰胺 、 N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 Boc-cysteine(4-Me-Bn) 、 N-叔丁氧羰基-N'-(2-氯苄氧羰基)-L-赖氨酸 、 N-叔丁氧羰基-O-(2-溴苄氧羰基)-L-酪氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 YGRKKRRQRRRC-NH₂
  参考文献：
  名称：

  Penetratin analogues acting as antifungal agents

  摘要：

  The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH2, a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.10.025

文献信息

• Penetratin analogues acting as antifungal agents
  作者：Francisco M. Garibotto、Adriana D. Garro、Ana M. Rodríguez、Marcela Raimondi、Susana A. Zacchino、Andras Perczel、Csaba Somlai、Botond Penke、Ricardo D. Enriz

  DOI：10.1016/j.ejmech.2010.10.025

  日期：2011.1

  The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH2, a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Acid-Active Cell-Penetrating Peptides for in Vivo Tumor-Targeted Drug Delivery
  作者：Erlei Jin、Bo Zhang、Xuanrong Sun、Zhuxian Zhou、Xinpeng Ma、Qihang Sun、Jianbin Tang、Youqing Shen、Edward Van Kirk、William J. Murdoch、Maciej Radosz

  DOI：10.1021/ja311180x

  日期：2013.1.16

  Cell-penetrating peptides (CPPs) such as transactivator of transcription (TAT) peptide have long been explored for promoting in vitro cell penetration and nuclear targeting of various cargos, but their positive charges cause strong nonspecific interactions, making them inapplicable for many in vivo applications. In this work, we used TAT to demonstrate a molecular modification approach for inhibiting nonspecific interactions of CPPs in the bloodstream while reactivating their functions in the targeted tissues or cells. The TAT lysine residues' amines were amidized to succinyl amides ((a)TAT), completely inhibiting TAT's nonspecific interactions in the blood compartment; once in the acidic tumor interstitium or internalized into cell endo/lysosomes, the succinyl amides in the (a)TAT were quickly hydrolyzed, fully restoring TAT's functions. Thus, (a)TAT-functionalized poly(ethylene glycol)-block-poly(epsilon-caprolactone) micelles achieved long circulation in the blood compartment and efficiently accumulated and delivered doxorubicin to tumor tissues, giving rise to high antitumor activity and low cardiotoxicity. This amidization strategy effectively and easily enables in vivo applications of CPPs.