前列腺素 J2 | 60203-57-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 前列腺素 J2
• 中文别名: 前列腺素J2
• 英文名称: prostaglandin J2
• 英文别名: PGJ2；(Z)-7-[(1S,5R)-5-[(E,3S)-3-hydroxyoct-1-enyl]-4-oxocyclopent-2-en-1-yl]hept-5-enoic acid
• CAS: 60203-57-8
• 化学式: C₂₀H₃₀O₄
• 分子量: 334.456
• InChiKey: UQOQENZZLBSFKO-POPPZSFYSA-N

物化性质

• 沸点：
  521.7±50.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：>100 mg/ml（来自 PGD2）； DMSO：>50 mg/ml（来自 PGD2）；乙醇：>75 mg/ml（来自 PGD2）； PBS pH 7.2：>2.7 mg/ml（来自 15-脱氧-.DEL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22,R36/37/38
• 安全说明：
  S26,S36

反应信息

• 作为反应物：
  描述：

  前列腺素 J2 在 human serum albumin 作用下， 反应 24.0h， 生成 15-deoxy-delta prostaglandin J2 、 Δ12-prostaglandin J2
  参考文献：
  名称：

  Δ¹²-Prostaglandin J₂ as a Product and Ligand of Human Serum Albumin: Formation of an Unusual Covalent Adduct at His146

  摘要：

  Human serum albumin (HSA), the most abundant protein in plasma, has a very unique function, catalyzing the conversion of prostaglandin J(2) (PGJ(2)), a dehydration product of PGD(2), to yield Delta(12)-PGJ(2). These PGD(2) metabolites are actively transported into cells and accumulated in the nuclei, where they act as potent inducers of cell growth inhibition and cell differentiation, and exhibit their own unique spectrum of biological effects. The facts that (i) arachidonic acid metabolites bind to human serum albumin (HSA) and the metabolism of these molecules is altered as a result of binding, (ii) HSA catalyzes the transformation of PGJ(2) into Delta(12)-PGJ(2), and (iii) Delta(12)-PGJ(2) is stable in serum suggest that HSA may bind and stabilize Delta(12)-PGJ(2) in a specific manner. A molecular interaction analysis using surface plasmon resonance (Biacore) indeed suggested the presence of a specific Delta(12)-PGJ(2)-binding site in HSA. To investigate the molecular details of the binding of this PGD(2) metabolite to albumin, we analyzed the cocrystal structure of the HSA-Delta(12)-PGJ(2)-myristate complex by X-ray crystallography and found that two Delta(12)-PGJ(2) molecules bind to a primary site in subdomain IB of the protein. The electron density results suggested that one of the two Delta(12)-PGJ(2) molecules that specifically bind to the site covalently interacted with a histidine residue (His146). Using nano-LC-MS/MS analysis of the HSA-Delta(12)-PGJ(2) Complex, the formation of an unusual Delta(12)-PGJ(2)-histidine adduct at His146 was confirmed. Thus, our crystallographic and mass spectrometric analyses of the HSA-Delta(12)-PGJ(2) complex provided intriguing new insights into the molecular details of how this electrophilic ligand interacts with its primary producer and transporter.

  DOI：

  10.1021/ja908878n
• 作为产物：
  描述：

  [3aR(3aα,4α,5β,6aα)]-(-)-5-(苯甲酰氧基)六氢-2-氧代-2H-环戊并[b]呋喃-4-甲醛 在 咪唑 、 4-二甲氨基吡啶 、 乙醇 、 三丁基膦 、 (-)-(S)-BINAL-H 、 氢氟酸 、 potassium tert-butylate 、 双氧水 、 sodium hydride 、 二异丁基氢化铝 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 138.25h， 生成 前列腺素 J2
  参考文献：
  名称：

  First Enantioselective Total Synthesis of (8S,12R,15S)-Prostaglandin J₂

  摘要：

  Enantioselective synthesis of natural PGJ(2) has been accomplished for the first time starting from the commercially available enantiopure aldehyde 7 in 10% overall yield. The key reaction was a novel prostaglandin class interconversion, i.e., an allylic 1,3-transposition across alcohol 9 derived from compound 14 in 73% overall yield. In principle, the unnatural enantiomer of PGJ(2) could be obtained starting from the commercially available enantiopure monobenzoate 7a following our strategy.

  DOI：

  10.1021/jo034502h

文献信息

• Enhancement of skin pigmentation by prostaglandins
  申请人：The Board of Regents of The University of Oklahoma

  公开号：US05905091A1

  公开（公告）日：1999-05-18

  A composition comprising a carrier and prostaglandin effective in stimulating synthesis of melanin in a human melanocyte thereby enhancing pigmentation of the human skin and optionally comprising a lysosomotropic agent, a phosphodiesterase inhibitor, and/or methylxanthines, and a method of use of the composition. Use of this composition promotes tanning of the human skin and increases photoprotection from ultraviolet radiation.

  本发明涉及一种组合物，包括一种载体和一种前列腺素，其在人体黑色素细胞中促进黑色素合成，从而增强人体皮肤的色素，并且还可以包括溶酶体靶向药物、磷酸二酯酶抑制剂和/或甲基黄嘌呤，并提供了使用该组合物的方法。使用该组合物可以促进人体皮肤晒黑，并增加对紫外线辐射的光保护。
• Use of prostaglandin A or its derivatives for the treatment of psoriasis
  申请人：Synphora AB

  公开号：EP1310256A2

  公开（公告）日：2003-05-14

  Prostaglandin A or derivatives thereof are effective to suppress cell growth and have utility in the treatment of psoriasis. The use of prostaglandin A or a derivative thereof for the manufacture of a medicament for the treatment of psoriasis, as well as a composition comprising a therapeutically active and physiologically acceptable amount thereof in a carrier.

  前列腺素 A 或其衍生物可有效抑制细胞生长，在治疗牛皮癣方面具有实用价值。前列腺素 A 或其衍生物可用于制造治疗银屑病的药物，以及在载体中含有治疗活性和生理可接受量的组合物。
• PROPHYLACTIC AGENT AND/OR THERAPEUTIC AGENT FOR CATARACT, MEDICINAL COMPOSITION FOR PREVENTING AND/OR TREATING CATARACT, USE OF PPAR ACTIVATOR FOR PRODUCING SAME, AND EYEDROPS
  申请人：University of Fukui

  公开号：EP3733203A1

  公开（公告）日：2020-11-04

  Provided are agents for prevention and therapeutic treatment of cataract that act by a different mechanism from conventional agents, and use of a PPAR activator for production of such agents. An agent for prevention and/or therapeutic treatment of cataract, containing a PPAR activator as an active ingredient, is used.

  本发明提供了预防和治疗白内障的药剂，其作用机理与传统药剂不同，还提供了使用 PPAR 激活剂生产此类药剂的方法。一种用于预防和/或治疗白内障的药剂含有 PPAR 激活剂作为活性成分。
• FGF21 C-terminal peptide optimization
  申请人：INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

  公开号：US11351268B2

  公开（公告）日：2022-06-07

  Disclosed herein are modified C-terminal fragments of FGF21 optimized for binding to Klotho β or antagonizing FGF21 activity. FGF21 peptides modified to comprise modifications to the C-terminal amino acid sequence are disclosed that have enhanced activity at the FGF21 receptor. Additionally, conjugates formed between the optimized FGF21 peptide fragments and insulin like peptides or nuclear hormone receptor ligands are provided.

  本文公开了经过修饰的 FGF21 C 端片段，这些片段经过优化，可与 Klotho β 结合或拮抗 FGF21 的活性。已公开的 FGF21 多肽包括对 C 端氨基酸序列的修饰，在 FGF21 受体上具有更强的活性。此外，还提供了优化的 FGF21 肽片段与胰岛素样肽或核激素受体配体之间形成的共轭物。
• Stereoselective Conjugation of Prostaglandin A₂ and Prostaglandin J₂ with Glutathione, Catalyzed by the Human Glutathione <i>S</i>-Transferases A1-1, A2-2, M1a-1a, and P1-1
  作者：Jan J. P. Bogaards、Joke C. Venekamp、Peter J. van Bladeren

  DOI：10.1021/tx9601770

  日期：1997.3.1

  Prostaglandins containing an alpha,beta-unsaturated keto group, such as prostaglandin A(2) (PGA(2)) and prostaglandin J(2) (PGJ(2)), inhibit cell proliferation. These cyclopentenone prostaglandins may be conjugated with GSH chemically or enzymatically via glutathione S-transferases, and this has been suggested to result in inhibition of the antiproliferative mode of action. In the present study, the role of the major human GSTs in the conjugation of PGA(2) and PGJ(2) with GSH was investigated with purified enzymes, i.e., the Alpha-class enzymes GST A1-1 and GST A2-2, the Mu-class enzyme GST M1a-1a, and the Pi-class enzyme GST P1-1. The GSH conjugates were separated from the parent compound by HPLC and identified by fast atom bombardment mass spectrometry and H-1-NMR. Two GSH conjugates were found for both PGA(2) and PGJ(2), the R- and S-GSH conjugates of both prostaglandins. Incubation experiments with PGA(2) and PGJ(2) (70-600 mu M) clearly showed the role of individual GSTs in the conjugation of PGA(2) and PGJ(2). Compared to the chemical reaction, enzyme activities towards PGA(2) were up to 5.4 times as high (GSTA1-1) at the lowest concentration (70 mu M), while at the highest concentration (600 mu M) enzyme activities were up to 3.0 times as high (GST P1-1). For PGJ(2), enzyme activities were Up to 4.3 (GSTM1a-1a, 70 mu M) and up to 3.1 (GSTM1a-1a, 600 mu M) times as high. As expected, similar amounts of the R- and S-conjugates of both prostaglandins were found in the chemical reaction. Striking stereoselectivities in conjugating activities were observed for GST A1-1 and GST P1-1. GST A1-1 favors the formation of the R-GSH conjugates of both prostaglandins. GST P1-1 showed a clear selectivity with regard to the formation of the S-GSH conjugate of PGA(2). However, this selectivity was not found for the formation of the S-GSH conjugate of PGJ(2). GSTM1a-1a showed no stereoselectivity with regard to the GSH conjugation of both PGA(2) and PGJ(2). GSTA2-2 only showed some minor formation of the R-GSH conjugate of PGJ(2). The possible implications of the observed stereoselectivity on the effects of PGA(2) and PGJ(2) are discussed.