H-Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-NH2 | 1609359-16-1

• 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: H-Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-NH2
• 英文别名: (2S)-2-amino-N-[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide
• CAS: 1609359-16-1
• 化学式: C₄₅H₈₀N₂₀O₁₁
• 分子量: 1077.26
• InChiKey: OFKZKTZPJFDNCH-DKTXOJPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.3
• 重原子数：
  76
• 可旋转键数：
  36
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  540
• 氢给体数：
  17
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 N-芴甲氧羰基-L-组氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 H-Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-NH2
  参考文献：
  名称：

  Identifying structural determinants of potency for analogs of apelin-13: Integration of C-terminal truncation with structure–activity

  摘要：

  Apelin peptides function as endogenous ligands of the APJ receptor and have been implicated in a number of important biological processes. While several apelinergic peptides have been reported, apelin-13 (Glu-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe) remains the most commonly studied and reported ligand of APJ. This study examines the effect of C-terminal peptide truncations and comprehensive structure-activity relationship (SAR) for a series of analogs based on apelin-13 in an attempt to develop more potent and stable analogs. C-terminal truncation studies identified apelin-13 (N-acetyl 2-11) amide (9) as a potent agonist (EC50 = 4.4 nM). Comprehensive SAR studies also determined that Arg-2, Leu-5, Lys-8, Met-11, were key positions for determining agonist potency, whereas the hydrophobic volume of Lys-8 was a specific determinate of activity. Plasma stability studies on the truncated 10-mer peptide 28 (EC50 = 33 nM) indicated the primary sites of cleavage occurred between Nle-3 and Leu-4 and also between Ala-5 and Ala-6. These new ligands represent the shortest known apelin peptides with good functional potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.001

文献信息

• Identifying structural determinants of potency for analogs of apelin-13: Integration of C-terminal truncation with structure–activity
  作者：Yanyan Zhang、Rangan Maitra、Danni L. Harris、Suraj Dhungana、Rodney Snyder、Scott P. Runyon

  DOI：10.1016/j.bmc.2014.04.001

  日期：2014.6

  Apelin peptides function as endogenous ligands of the APJ receptor and have been implicated in a number of important biological processes. While several apelinergic peptides have been reported, apelin-13 (Glu-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe) remains the most commonly studied and reported ligand of APJ. This study examines the effect of C-terminal peptide truncations and comprehensive structure-activity relationship (SAR) for a series of analogs based on apelin-13 in an attempt to develop more potent and stable analogs. C-terminal truncation studies identified apelin-13 (N-acetyl 2-11) amide (9) as a potent agonist (EC50 = 4.4 nM). Comprehensive SAR studies also determined that Arg-2, Leu-5, Lys-8, Met-11, were key positions for determining agonist potency, whereas the hydrophobic volume of Lys-8 was a specific determinate of activity. Plasma stability studies on the truncated 10-mer peptide 28 (EC50 = 33 nM) indicated the primary sites of cleavage occurred between Nle-3 and Leu-4 and also between Ala-5 and Ala-6. These new ligands represent the shortest known apelin peptides with good functional potency. (C) 2014 Elsevier Ltd. All rights reserved.