deamino-Lys-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH | 1439656-62-8

• 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: deamino-Lys-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH
• 英文别名: (3S)-3-(6-aminohexanoylamino)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
• CAS: 1439656-62-8
• 化学式: C₅₆H₈₂N₁₄O₁₃
• 分子量: 1159.35
• InChiKey: DLGOQWJOTFVAGW-ISXIHVMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  83
• 可旋转键数：
  35
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  438
• 氢给体数：
  14
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  deamino-Lys-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH 、 3,4-二甲氧基-3-环丁烯-1,2-二酮 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 (3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[6-[(2-methoxy-3,4-dioxocyclobuten-1-yl)amino]hexanoylamino]-4-oxobutanoic acid
  参考文献：
  名称：

  Bivalent angiotensin II suppresses oxidative stress-induced hyper-responsiveness of angiotensin II receptor type I

  摘要：

  Angiotensin II receptor type I (AT(1)R) is a G-protein coupled receptor involved in regulation of body water-electrolyte balance and blood pressure. Oxidative stress promotes AT(1)R oligomerization and hyper-responsiveness to its cognate ligand Ang II. In this study, bivalent Ang II, synthesized by linking with aminocaproic acid (Acp) at the N-terminus, was used to induce AT(1)R dimerization and hyper-responsiveness in AT(1)R-expressed human embryonic kidney (AT(1)R-HEK) cells, determined using image correlation spectroscopy (ICS) and by measuring AT(1)R-mediated change in intracellular Ca2+ concentration, respectively. In addition, ICS was employed to determine distribution pattern of cell-surface AT(1)R and its degree of aggregation when stimulated by monomeric (monovalent) and bivalent Ang II under oxidative stress (100 mu M H2O2) condition in comparison with normal (unoxidized) AT(1)R-HEK cells. Bivalent Ang II induced cell-surface AT(1)R aggregation/clustering but maintained AT(1)R normal signaling response under oxidative stress condition, whereas stimulation by monomeric Ang II or a mixture of monomeric and Acp-modified Ang II (used in the synthesis of bivalent form) resulted in AT(1)R hyper-responsiveness. These results suggest that bivalent ligand (viz. Ang II) provides another strategy in the development of novel drugs specifically designed for attenuating aberrant responsiveness of cognate receptor (AT(1)R) under pathological (oxidative stress) conditions. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.041

文献信息

• Bivalent angiotensin II suppresses oxidative stress-induced hyper-responsiveness of angiotensin II receptor type I
  作者：Titiwat Sungkaworn、Chutima Jiarpinitnun、Pongkorn Chaiyakunvat、Varanuj Chatsudthipong

  DOI：10.1016/j.ejmech.2013.02.041

  日期：2013.5

  Angiotensin II receptor type I (AT(1)R) is a G-protein coupled receptor involved in regulation of body water-electrolyte balance and blood pressure. Oxidative stress promotes AT(1)R oligomerization and hyper-responsiveness to its cognate ligand Ang II. In this study, bivalent Ang II, synthesized by linking with aminocaproic acid (Acp) at the N-terminus, was used to induce AT(1)R dimerization and hyper-responsiveness in AT(1)R-expressed human embryonic kidney (AT(1)R-HEK) cells, determined using image correlation spectroscopy (ICS) and by measuring AT(1)R-mediated change in intracellular Ca2+ concentration, respectively. In addition, ICS was employed to determine distribution pattern of cell-surface AT(1)R and its degree of aggregation when stimulated by monomeric (monovalent) and bivalent Ang II under oxidative stress (100 mu M H2O2) condition in comparison with normal (unoxidized) AT(1)R-HEK cells. Bivalent Ang II induced cell-surface AT(1)R aggregation/clustering but maintained AT(1)R normal signaling response under oxidative stress condition, whereas stimulation by monomeric Ang II or a mixture of monomeric and Acp-modified Ang II (used in the synthesis of bivalent form) resulted in AT(1)R hyper-responsiveness. These results suggest that bivalent ligand (viz. Ang II) provides another strategy in the development of novel drugs specifically designed for attenuating aberrant responsiveness of cognate receptor (AT(1)R) under pathological (oxidative stress) conditions. (C) 2013 Elsevier Masson SAS. All rights reserved.