人牛吡啶Apelin-13 | 217082-60-5

• 物质功能分类: 生物化工 - 多肽
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 人牛吡啶Apelin-13
• 中文别名: 人牛吡啶APELIN-13
• 英文名称: pyr-1-apelin-13
• 英文别名: pyr apelin-13；pERPRLSHKGPMPF；Pyr-R-P-R-L-S-H-K-G-P-M-P-F；[Pyr1]-Apelin-13；(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 217082-60-5
• 化学式: C₆₉H₁₀₈N₂₂O₁₆S
• 分子量: 1533.82
• InChiKey: GGMAXEWLXWJGSF-PEWBXTNBSA-N

物化性质

• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  108
• 可旋转键数：
  44
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  618
• 氢给体数：
  18
• 氢受体数：
  21

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

[Pyr1]-Apelin-13 是一种高效的、选择性的内源性 apelin 受体激动剂。

体外研究

[Pyr1]-apelin-13 包封在脂质体聚乙二醇颗粒 (lipoPEG-PA13) 中，在生理条件下能够实现持续和延长的药物释放。

体内研究

在压力过载诱导心力衰竭的小鼠模型中，[Pyr1]-apelin-13 纳米载体表现出长期可持续的效果，有助于预防心脏功能障碍。研究发现，[Pyr1] apelin-13 (1 μg 和 5 μg) 可以改善小鼠的运动行为并减轻疼痛症状、减少囊腔大小和 caspase-3 水平。此外，1 μg 和 5 μg 的 [Pyr1] apelin-13 显著增加热足部撤回潜伏期，并在第二周后显著降低术后神经损伤动物的足部撤回阈值。

参考质量标准

• 外观：白色粉末
• 纯度 (HPLC) ≥98.0%
• 醋酸根含量 ≤12.0%
• 水分含量 ≤8.0%
• 肽含量 ≥80.0%
• 内毒素 ≤50EU/mg
• 氨基酸组成分析 ≤±10%

反应信息

• 作为反应物：
  描述：

  人牛吡啶Apelin-13 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (2R)-2-[(2R)-2-[(2S)-2-hydroxypropanoyl]oxypropanoyl]oxypropanoic acid
  参考文献：
  名称：

  Solid-phase synthesis of enantio-controlled lactic acid oligomers

  摘要：

  A synthetic method for lactic acid oligomers via solid-phase synthesis under mild reaction conditions with up to 99% yield is presented. The fine control of the chirality on each lactic acid unit of the oligomers was easily achieved by the substitution of (R)-THP-protected lactic acid (R)-2 by (S)-2 without alternating the procedure. The overall synthesis of the trimer and tetramer was completed in one and two days, respectively. Intramolecular cyclizations of enantio-controlled lactic acids were also attempted through the Yamaguchi macrolactonization or the Mitsunobu reaction. However, we were unable to isolate single cyclic oligomers but always obtained a mixture of cyclic oligomers. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.08.021
• 作为产物：
  描述：

  (2R)-2-[(2R)-2-[(2R)-2-hydroxypropanoyl]oxypropanoyl]oxypropanoic acid 在 甲醇 、 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 人牛吡啶Apelin-13
  参考文献：
  名称：

  Solid-phase synthesis of enantio-controlled lactic acid oligomers

  摘要：

  A synthetic method for lactic acid oligomers via solid-phase synthesis under mild reaction conditions with up to 99% yield is presented. The fine control of the chirality on each lactic acid unit of the oligomers was easily achieved by the substitution of (R)-THP-protected lactic acid (R)-2 by (S)-2 without alternating the procedure. The overall synthesis of the trimer and tetramer was completed in one and two days, respectively. Intramolecular cyclizations of enantio-controlled lactic acids were also attempted through the Yamaguchi macrolactonization or the Mitsunobu reaction. However, we were unable to isolate single cyclic oligomers but always obtained a mixture of cyclic oligomers. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.08.021

文献信息

• Linking (Pyr)1apelin-13 pharmacokinetics to efficacy: Stabilization and measurement of a high clearance peptide in rodents
  作者：Joelle M. Onorato、Carrie Xu、Xue-Qing Chen、Anne V. Rose、Claudia Generaux、Kimberley Lentz、Petia Shipkova、Susan Arthur、James K. Hennan、Roy Haskell、Michael C. Myers、R. Michael Lawrence、Heather J. Finlay、Michael Basso、Jeffrey Bostwick、Gayani Fernando、Ricardo Garcia、Samuel Hellings、Mei-Yin Hsu、Rongan Zhang、Lei Zhao、Peter Gargalovic

  DOI：10.1016/j.ab.2018.12.022

  日期：2019.3

  Apelin, the endogenous ligand for the APJ receptor, has generated interest due to its beneficial effects on the cardiovascular system. Synthesized as a 77 amino acid preproprotein, apelin is post-translationally cleaved to a series of shorter peptides. Though (Pyr)(1) apelin-13 represents the major circulating form in plasma, it is highly susceptible to proteolytic degradation and has an extremely short half-life, making it challenging to quantify. Literature reports of apelin levels in rodents have historically been determined with commercial ELISA kits which suffer from a lack of selectivity, recognizing a range of active and inactive isoforms of apelin peptide. (Pyr)(1) apelin-13 has demonstrated beneficial hemodynamic effects in humans, and we wished to evaluate if similar effects could be measured in pre-clinical models. Despite development of a highly selective LC/MS/MS method, in rodent studies where (Pyr)(1) apelin-13 was administered exogenously the peptide was not detectable until a detailed stabilization protocol was implemented during blood collection. Further, the inherent high clearance of (Pyr)(1) apelin-13 required an extended release delivery system to enable chronic dosing. The ability to deliver sustained doses and stabilize (Pyr)(1) apelin-13 in plasma allowed us to demonstrate for the first time the link between systemic concentration of apelin and its pharmacological effects in animal models.
• 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.
• C-Terminal Modifications of Apelin-13 Significantly Change Ligand Binding, Receptor Signaling, and Hypotensive Action
  作者：Alexandre Murza、Élie Besserer-Offroy、Jérôme Côté、Patrick Bérubé、Jean-Michel Longpré、Robert Dumaine、Olivier Lesur、Mannix Auger-Messier、Richard Leduc、Philippe Sarret、Éric Marsault

  DOI：10.1021/jm501916k

  日期：2015.3.12

  Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family. This system plays an important role in the regulation of blood pressure and cardiovascular functions. To better understand the role of its C-terminal Phe13 residue on ligand binding, receptor signaling, and hypotension, we report a series of modified analogues in which Phe13 was substituted by unnatural amino acids. These modifications delivered new compounds exhibiting higher affinity and potency to inhibit cAMP accumulation compared to apelin-13. In particular, analogues Bpa(13) or (alpha-Me)Phe(13) were 30-fold more potent to inhibit cAMP accumulation than apelin-13. Tyr(OBn)(13) substitution led to a 60-fold improvement in binding affinity and induced stronger and more sustained drop in blood pressure compared to apelin-13. Our study identified new potent analogues of apelin-13, which represent valuable probes to better understand its structurefunction relationship.
• Solid-phase synthesis of enantio-controlled lactic acid oligomers
  作者：Seong-Ho Kim、Yong-Kyun Sim、Bum-Tae Kim、Yong Hwan Kim、Yeong-Joon Kim、Seongsoon Park、Hyuk Lee

  DOI：10.1016/j.tetasy.2011.08.021

  日期：2011.7

  A synthetic method for lactic acid oligomers via solid-phase synthesis under mild reaction conditions with up to 99% yield is presented. The fine control of the chirality on each lactic acid unit of the oligomers was easily achieved by the substitution of (R)-THP-protected lactic acid (R)-2 by (S)-2 without alternating the procedure. The overall synthesis of the trimer and tetramer was completed in one and two days, respectively. Intramolecular cyclizations of enantio-controlled lactic acids were also attempted through the Yamaguchi macrolactonization or the Mitsunobu reaction. However, we were unable to isolate single cyclic oligomers but always obtained a mixture of cyclic oligomers. (C) 2011 Elsevier Ltd. All rights reserved.