2-acetylamino-3-(3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenylsulfanyl)-propionic acid methyl ester | 142923-97-5

• 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: 2-acetylamino-3-(3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenylsulfanyl)-propionic acid methyl ester
• 英文别名: N-acetyl cystein (S-geranylgeranyl) methyl ester；N-acetyl-S-(geranylgeranyl)cysteine methyl ester；N-acetyl-S-geranylgeranyl-l-cysteine methyl ester；methyl (2R)-2-acetamido-3-[(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl]sulfanylpropanoate
• CAS: 142923-97-5
• 化学式: C₂₆H₄₃NO₃S
• 分子量: 449.698
• InChiKey: VGTWOXLGECENAG-KSRUOGSASA-N

物化性质

• 沸点：
  584.4±50.0 °C(Predicted)
• 密度：
  0.988±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  31
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-acetylamino-3-(3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenylsulfanyl)-propionic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以89%的产率得到N-acetyl cysteine (S-geranylgeranyl)
  参考文献：
  名称：

  Synthesis of high specific activity 35S-labelled N-methanesulfonyl farnesylcysteine and a photoactive analog

  摘要：

  前烯丙基化半胱氨酸类似物模拟前烯丙基化 GTP 结合蛋白（G 蛋白）的前烯丙基化半胱氨酸残基，已被广泛用于研究前烯丙基化 G 蛋白的行为。在这一领域的早期研究中，我们制备了光活性类似物 [35S]4，并证明它能在光解时标记 RhoGDI；这些结果与 GDI 包含异肾上腺素结合位点的观点一致。在此，我们介绍了 N-乙酰法尼基半胱氨酸及其甲酯的[35S]N-甲磺酰基标记类似物（1a 和 2a）的制备过程，以及光活性类似物 3 和 4 的改进合成过程；其比活性达到了 1100 Ci/mmol。未标记的化合物 1a 和 2a 被用作光解反应的竞争者，表明甲磺酰胺基是一种合理的乙酰胺取代基。其他实验表明，光活性酯 [35S]3 可以交联纯化形式和粗细菌提取物中的 GDI。然而，使用酯（[35S]3）获得的交联程度明显低于使用游离酸（[35S]4）观察到的交联程度，尽管酯化形式可能更接近于反映前炔化蛋白质 C 端的结构；使用 GDI-Cdc42 共晶体结构，讨论了这些结果的结构基础。Copyright © 2002 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.638
• 作为产物：
  描述：

  香叶基香叶醇 在 四溴化碳 、 zinc diacetate 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2-acetylamino-3-(3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenylsulfanyl)-propionic acid methyl ester
  参考文献：
  名称：

  A Photoactivatable Prenylated Cysteine Designed to Study Isoprenoid Recognition

  摘要：

  Protein prenylation, involving the alkylation of a specific C-terminal cysteine with a C-15 or C-20 isoprenoid unit, is an essential posttranslational modification required by most GTP-binding proteins for normal biological activity. Despite the ubiquitous nature of this modification and numerous efforts aimed at inhibiting prenylating enzymes for therapeutic purposes, the function of prenylation remains unclear. To explore the role the isoprenoid plays in mediating protein-protein recognition, we have synthesized a photoactivatable, isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C-terminus of prenylated proteins. Photolysis experiments with 2 and RhoCDI (GDI), a protein which interacts with prenylated Rho proteins, suggest that the GDI is in direct contact with the isoprenoid moiety. These results, obtained using purified GDI as well as Escherichia coli (E. coli) crude extract containing GDI, suggest that this analogue will be an effective and versatile tool for the investigation of putative isoprenoid binding sites in a variety of systems. Incorporation of this analogue into peptides or proteins should allow for even more specific interactions between the photoactivatable isoprenoid and any number of isoprenoid binding proteins.

  DOI：

  10.1021/ja0012016

文献信息

• Didehydrogeranylgeranyl (ΔΔGG):  A Fluorescent Probe for Protein Prenylation
  作者：Xiao-hui Liu、Glenn D. Prestwich

  DOI：10.1021/ja0119144

  日期：2002.1.1

  The first intrinsically fluorescent analog of geranylgeraniol, (2E,6E,8E,10E,12E,14E)-geranylgeraniol (all-trans-DeltaDeltaGGOH.1) has been synthesized stereoselectively and shown to substitute for the geranylgeranyl (GG) moiety in prenyl transferase reactions and in protein-ligand binding assays. All-trans-DeltaDeltaGGOH 1 showed blue fluorescence in methanol, with lambdaex = 310 nm and lambdaem = 410 nm (epsilon310 = 2.4 x 104 M-1 cm-1), but was only weakly fluorescent in aqueous solution. The prenyl transferase efficiency for DeltaDeltaGGPP 2 as a substrate for yeast protein geranylgeranyl transferase (PGGTase-I) was 60% relative to that for GGPP. The binding of DeltaDeltaGG-AcCysMe 3 to the recombinant Rho GTPase dissociation inhibitor (RhoGDI) had a KD of 15.1 +/- 1.2 muM, 6-fold lower than the affinity of GG-AcCysMe. Thus, the DeltaDeltaGG moiety is a novel fluorophore suitable for studying the interaction and subcellular localization of prenylated small GTPase proteins in signaling complexes.
• A Photoactivatable Prenylated Cysteine Designed to Study Isoprenoid Recognition
  作者：Tamara A. Kale、Conrad Raab、Nathan Yu、Dennis C. Dean、Mark D. Distefano

  DOI：10.1021/ja0012016

  日期：2001.5.1

  Protein prenylation, involving the alkylation of a specific C-terminal cysteine with a C-15 or C-20 isoprenoid unit, is an essential posttranslational modification required by most GTP-binding proteins for normal biological activity. Despite the ubiquitous nature of this modification and numerous efforts aimed at inhibiting prenylating enzymes for therapeutic purposes, the function of prenylation remains unclear. To explore the role the isoprenoid plays in mediating protein-protein recognition, we have synthesized a photoactivatable, isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C-terminus of prenylated proteins. Photolysis experiments with 2 and RhoCDI (GDI), a protein which interacts with prenylated Rho proteins, suggest that the GDI is in direct contact with the isoprenoid moiety. These results, obtained using purified GDI as well as Escherichia coli (E. coli) crude extract containing GDI, suggest that this analogue will be an effective and versatile tool for the investigation of putative isoprenoid binding sites in a variety of systems. Incorporation of this analogue into peptides or proteins should allow for even more specific interactions between the photoactivatable isoprenoid and any number of isoprenoid binding proteins.
• Synthesis of high specific activity 35S-labelled N-methanesulfonyl farnesylcysteine and a photoactive analog
  作者：Tamara A. Kale、Conrad Raab、Nathan Yu、Evelyn Aquino、Dennis C. Dean、Mark D. Distefano

  DOI：10.1002/jlcr.638

  日期：2003.1

  Prenylated cysteine analogs, which mimic the prenylated cysteine residue of prenylated GTP-binding proteins (G-proteins), have been used in a variety of contexts for the study of prenylated G-protein behavior. In earlier work in this area, we prepared the photoactive analog [35S]4 and showed that it labelled RhoGDI upon photolysis; those results were consistent with the idea that GDI contains an isoprenoid binding site. Here, we describe the preparation of [35S]N-methanesulfonyl labelled analogs (1a and 2a) of N-acetyl farnesylcysteine and its methyl ester together with an improved synthetic procedure for photoactive analogs 3 and 4; specific activities of ∼1100 Ci/mmol were achieved. Compounds 1a and 2a in unlabelled form were used as competitors in photolysis reactions to show that the methanesulfonamido group is a reasonable acetamide substitution. Additional experiments show that the photoactive ester [35S]3 can cross-link GDI in both purified form and crude bacterial extract. However, the extent of cross-linking obtained with the ester ([35S]3) is significantly less than that observed with the free acid ([35S]4) despite the fact that the esterified form probably more closely reflects the structure of the C-terminus of a prenylated protein; using the GDI·Cdc42 co-crystal structure, the structural basis for these results is discussed. Copyright © 2002 John Wiley & Sons, Ltd.

  前烯丙基化半胱氨酸类似物模拟前烯丙基化 GTP 结合蛋白（G 蛋白）的前烯丙基化半胱氨酸残基，已被广泛用于研究前烯丙基化 G 蛋白的行为。在这一领域的早期研究中，我们制备了光活性类似物 [35S]4，并证明它能在光解时标记 RhoGDI；这些结果与 GDI 包含异肾上腺素结合位点的观点一致。在此，我们介绍了 N-乙酰法尼基半胱氨酸及其甲酯的[35S]N-甲磺酰基标记类似物（1a 和 2a）的制备过程，以及光活性类似物 3 和 4 的改进合成过程；其比活性达到了 1100 Ci/mmol。未标记的化合物 1a 和 2a 被用作光解反应的竞争者，表明甲磺酰胺基是一种合理的乙酰胺取代基。其他实验表明，光活性酯 [35S]3 可以交联纯化形式和粗细菌提取物中的 GDI。然而，使用酯（[35S]3）获得的交联程度明显低于使用游离酸（[35S]4）观察到的交联程度，尽管酯化形式可能更接近于反映前炔化蛋白质 C 端的结构；使用 GDI-Cdc42 共晶体结构，讨论了这些结果的结构基础。Copyright © 2002 John Wiley & Sons, Ltd. All Rights Reserved.