methyl S-farnesylcysteine | 130062-64-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl S-farnesylcysteine
• 英文别名: S-farnesyl-L-cysteine methyl ester；S-(farnesyl)cysteine methyl ester；L-S-(trans,trans-farnesyl)cysteine methyl ester；Farnesylcysteine methyl ester；methyl (2R)-2-amino-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoate
• CAS: 130062-64-5
• 化学式: C₁₉H₃₃NO₂S
• 分子量: 339.543
• InChiKey: SIEHZFPZQUNSAS-GCVUPTOQSA-N

物化性质

• 沸点：
  446.7±45.0 °C(Predicted)
• 密度：
  0.987±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl S-farnesylcysteine 在 哌啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 达卡巴嗪 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 生成 H-Cys(StBu)-Met-Gly-Leu-Pro-Cys((E,E)-farnesyl)-OMe
  参考文献：
  名称：

  Efficient Synthesis of a Fluorescent Farnesylated Ras Peptide

  摘要：

  DOI：

  10.1021/jo015526w
• 作为产物：
  描述：

  反式,反式-金合欢醇 在 氨 、 三溴化磷 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 2.0h， 生成 methyl S-farnesylcysteine
  参考文献：
  名称：

  Polyisoprenylated methylated protein methyl esterase: A putative biomarker and therapeutic target for pancreatic cancer

  摘要：

  Pancreatic cancer is the most deadly neo plasm with a 5-year survival rate of less than 6%. Over 90% of cases harbor K-Ras mutations, which are the most challenging to treat due to lack of effective therapies. Here, we reveal that polyisoprenylated methylated protein methyl esterase (PMPMEase) is overexpressed in 93% of pancreatic ductal adenocarcinoma. We further present polyisoprenylated cysteinyl amide inhibitors (PCAIs) as novel compounds designed with structural elements for optimal in vivo activities and selective disruption of polyisoprenylation-mediated protein functions. The PCAIs inhibited PMPMEase with K-i values ranging from 3.7 to 20 mu M. The 48 h E-50 values for pancreatic cancer Mia PaCa-2 and BxPC-3 cell lines were as low as 1.9 mu M while salirasib and farnesylthiosalicylamide were ineffective at 20 mu M. The PCAIs thus have the potential to serve as effective therapies for pancreatic and other cancers with hyperactive growth signaling pathways mediated by Ras and related G-proteins. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.018

文献信息

• Synthesis and Evaluation of Acyl Protein Thioesterase 1 (APT1) Inhibitors
  作者：Markus Biel、Patrick Deck、Athanassios Giannis、Herbert Waldmann

  DOI：10.1002/chem.200501128

  日期：2006.5.15

  Recently, an enzyme, acyl protein thioesterase 1 (APT1), that may play a regulatory role in the palmitoylation cycle of H-Ras and G-protein alpha subunits, was purified. Motivated by this work, several inhibitors of APT1 were designed, synthesized and biologically evaluated leading to highly active compounds.

  脂质修饰的蛋白质在重要的生物学过程中起着决定性作用，例如信号转导，细胞骨架的组织和囊泡转运。这些蛋白质的脂化对于正确的生物学功能是必不可少的。在脂质修饰中，烯丙基化和肉豆蔻酰基化是众所周知的。但是，棕榈酰化的机制仍在研究中。最近，纯化了一种可能在H-Ras和G蛋白α亚基的棕榈酰化循环中起调节作用的酰基蛋白硫酯酶1（APT1）酶。受这项工作的启发，设计，合成了多种APT1抑制剂，并对其进行了生物学评估，从而产生了高活性的化合物。
• [EN] ISOPRENYL COMPOUNDS AND METHODS THEREOF<br/>[FR] COMPOSÉS ISOPRÉNYLÉS ET LEURS PROCÉDÉS
  申请人：SIGNUM BIOSCIENCES INC

  公开号：WO2010056778A1

  公开（公告）日：2010-05-20

  Among other things, the present invention provides novel isoprenyl compounds capable of effectively modulating inflammatory responses and pharmaceutical, cosmetic, cosmeceutical and topical compositions comprising these isoprenyl compounds. Anti-inflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with inflammation. Proinflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with suppression of inflammatory responses. Thus, the present invention also provides methods useful in the treatment or prevention of diseases or conditions associated with inflammation as well as methods useful in the treatment or prevention of diseases or conditions associated with suppression of inflammatory responses.

  除其他事项外，本发明提供了能够有效调节炎症反应的新异戊二烯化合物，以及包含这些异戊二烯化合物的药用、化妆品、护肤品和局部组合物。本发明的抗炎化合物在治疗或预防与炎症相关的疾病或症状方面是有用的。本发明的促炎化合物在治疗或预防与抑制炎症反应相关的疾病或症状方面是有用的。因此，本发明还提供了在治疗或预防与炎症相关的疾病或症状以及在治疗或预防与抑制炎症反应相关的疾病或症状方面有用的方法。
• Synthesis of Functional <i>Ras</i> Lipoproteins and Fluorescent Derivatives
  作者：Karsten Kuhn、David J. Owen、Benjamin Bader、Alfred Wittinghofer、Jürgen Kuhlmann、Herbert Waldmann

  DOI：10.1021/ja002723o

  日期：2001.2.1

  protein. Furthermore, a preliminary study on the biological activity of the natural Ras protein derivative (containing the normal farnesyl and palmitoyl lipid residues) has shown full biological activity. This result highlights the usefulness of these compounds as invaluable tools for the study of Ras signal transduction processes and the plasma membrane localization of the Ras proteins.

  对于生物信号转导的研究，获得正确脂化的蛋白质至关重要。此外，获得包含正确蛋白质结构但可能额外携带不同脂质基团或标记（即荧光标签）的生物缀合物，通过这些标记可以在生物系统中追踪蛋白质，可以提供宝贵的试剂。我们在此报告一系列修饰 Ras 蛋白合成技术的发展。这些经过修饰的 Ras 蛋白携带许多不同的天然和非天然脂质残基，并且该过程还扩展为还提供了获得许多荧光标记衍生物的途径。马来酰亚胺基团提供了以特定和有效方式将化学合成的脂肽分子连接到截短形式的 H-Ras 蛋白的关键。此外，对天然 Ras 蛋白衍生物（含有正常法呢基和棕榈酰脂质残基）的生物活性的初步研究已显示出完整的生物活性。这一结果突出了这些化合物作为研究 Ras 信号转导过程和 Ras 蛋白的质膜定位的宝贵工具的有用性。
• Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity
  作者：David A Perrey、Rama Krishna Narla、Fatih M Uckun

  DOI：10.1016/s0960-894x(00)00046-9

  日期：2000.3

  diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low micromolar range. The best compounds were N-acetyl-S-dodecyl-Cys chloromethyl ketone (IC50 = 2.0 microM against

  合成了一系列半胱氨酸重氮甲基和氯甲基酮衍生物，并针对人的B谱系（Nalm-6）和T谱系（Molt-3）急性淋巴细胞白血病细胞系进行了评估。氯甲基酮化合物显示出对这些细胞系的有效细胞毒性，IC50值在低微摩尔范围内。最好的化合物是N-乙酰基-S-十二烷基-Cys氯甲基酮（对Nalm-6的IC50 = 2.0 microM，对Molt-3的IC50 = 2.3 microM）和N-乙酰-S-反式，反-法呢基-Cys氯甲基酮（IC50相对于Nalm-6为3.0 microM，针对Molt-3为1.4 microM）。
• Method for Preparing Isoprenyl Cysteine Compounds and Analogs Thereof
  申请人：Rapole Keshava

  公开号：US20090192332A1

  公开（公告）日：2009-07-30

  Methods of preparing isoprenyl cysteine compounds by coupling a cysteine compound with an activated (i.e. halogenated) lipid are disclosed. Also disclosed, among other things, are methods of making activated (i.e. halogenated) lipids, and methods of purifying isoprenyl cysteine compounds.

  通过将半胱氨酸化合物与活化的（即卤代的）脂质偶联，可以制备异戊基半胱氨酸化合物的方法已被披露。此外，还披露了制备活化的（即卤代的）脂质的方法，以及纯化异戊基半胱氨酸化合物的方法。