(BocGly)2Cys2(OAll)2 | 212119-85-2

• 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: (BocGly)2Cys2(OAll)2
• 英文别名: N,N-bis-(tert-butyloxycarbonyl-glycyl)-L-cystine bis-allyl ester；bis(N-tert-butyloxycarbonyl-L-glycyl)-L-cystine bis(allyl ester)；bis-(N-tert-butyloxycarbonyl-glycyl)-L-cystine bis(allyl ester)；bis-(N-tert-butyloxycarbonylglycyl)-L-cystine bis-(allyl ester)；Bis(N-tert-butoxycarbonylglycyl)-L-cystine bisallyl ester；(Boc-Gly-Cys-OAll)2
• CAS: 212119-85-2
• 化学式: C₂₆H₄₂N₄O₁₀S₂
• 分子量: 634.772
• InChiKey: KAOLFDVEIVAGNO-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.85
• 重原子数：
  42.0
• 可旋转键数：
  17.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  187.46
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (BocGly)2Cys2(OAll)2 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 DL-dithiothreitol 作用下， 以 四氢呋喃 为溶剂， 生成 N-tert-butyloxycarbonyl-glycyl-(S-palmitoyl)-L-cysteine
  参考文献：
  名称：

  功能性 Ras 脂蛋白和荧光衍生物的合成

  摘要：

  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。

  DOI：

  10.1021/ja002723o
• 作为产物：
  描述：

  BOC-甘氨酸 、 L-Cystine bisallyl ester bis(toluene-4-sulfonate) 在 1-羟基苯并三唑 、 达卡巴嗪 作用下， 以97%的产率得到(BocGly)2Cys2(OAll)2
  参考文献：
  名称：

  Chemoenzymatic Synthesis of N-Ras Lipopeptides

  摘要：

  For the study of biological phenomena influenced by the plasma-membrane-bound Ras proteins and other lipidated proteins, characteristic peptides which embody the correct lipid modifications of their parent proteins (palmitoyl thioesters and farnesyl thioethers), as well as analogues thereof, may serve as suitable tools. For the construction of such acid- and base-labile peptide conjugates, the enzyme-labile p-acetoxybenzyloxycarbonyl (AcOZ) urethane blocking group was developed. The acetate moiety within the AcOZ group is easily saponified by treatment with acetyl esterase or lipase. After cleavage of the acetate group the resulting quinone methide spontaneously fragments, resulting in the liberation of the desired peptide or peptide conjugates. This enzymatic protecting group technique formed the key step in the synthesis of the characteristic S-palmitoylated and S-farnesylated C-terminus of the human N-Ras protein. Deprotections are so mild that no undesired side reactions of the lipid conjugates are observed (i.e., no hydrolysis or beta-elimination of the thioester and no acid-mediated attack on the double bonds of the farnesyl group). The combination of enzymatic protecting group techniques with classical chemical methods allowed access to various fluorescent-labeled and differently lipid-modified Rns lipopeptides. Their application in biological experiments enabeled the study of the structural requirements for the acylation of Ras sequence motifs in vivo and gave insight into the subcellular site at which these modifications occur. The results indicate that the plasma membrane is a major site of cellular S-acylation. This supports a mechanism for the selective subcellular localization of lipidated proteins, including the Rns proteins themselves, by kinetic targeting to the plasma membrane.

  DOI：

  10.1021/ja9805627

文献信息

• Cotte, Alain; Bader, Benjamin; Kuhlmann, Juergen, Chemistry - A European Journal, 1999, vol. 5, # 3, p. 922 - 936
  作者：Cotte, Alain、Bader, Benjamin、Kuhlmann, Juergen、Waldmann, Herbert

  DOI：——

  日期：——
• Synthesis of the palmitoylated and prenylated C-terminal lipopeptides of the human R- and N-Ras proteins
  作者：T. Schmittberger、H. Waldmann

  DOI：10.1016/s0968-0896(98)00251-x

  日期：1999.5

  For the study of biological phenomena influenced by the R- and N-Ras proteins, characteristic peptides which embody the correct lipid modifications of their parent proteins (palmitoyl thioesters, geranylgeranyl thioethers, and farnesyl thioethers), as well as analogues thereof, may serve as efficient tools. For the construction of such acid- and base labile peptide conjugates the allyl ester was developed as C-terminal protecting group. Allyl esters are cleaved selectively and in high yields from lipidated peptides by Pd(0)-mediated allyl transfer to accepting N- or C-nucleophiles like morpholine and N,N-dimethylbarbituric acid. This protecting group technique formed the key step in the synthesis of the characteristic S-palmitoylated and S-isoprenylated C-terminus of human R-Ras and human N-Ras proteins, as well as several analogues thereof. Deprotections are so mild that no undesired side reactions of the lipid conjugates are observed. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Schelhaas, Michael; Naegele, Edgar; Kuder, Norman, Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1239 - 1252
  作者：Schelhaas, Michael、Naegele, Edgar、Kuder, Norman、Bader, Benjamin、Kuhlmann, Juergen、Wittinghofer, Alfred、Waldmann, Herbert

  DOI：——

  日期：——
• Lipid Modifications of a Ras Peptide Exhibit Altered Packing and Mobility versus Host Membrane as Detected by ²H Solid-State NMR
  作者：Alexander Vogel、Catherine P. Katzka、Herbert Waldmann、Klaus Arnold、Michael F. Brown、Daniel Huster

  DOI：10.1021/ja051856c

  日期：2005.9.1

  The human N-ras protein binds to cellular membranes by insertion of two covalently bound posttranslational lipid modifications, which is crucial for its function in signal transduction and cell proliferation. Mutations in ras may lead to unregulated cell growth and eventually cancer, making it an important therapeutic target. Here we have investigated the molecular details of the membrane binding mechanism. A heptapeptide derived from the C-terminus of the human N-ras protein was synthesized including two hexadecyl modifications. Solid-state H-2 NMR was used to determine the packing and molecular dynamics of the ras lipid chains as well as the phospholipid matrix. Separately labeling the chains of the peptide and the phospholipids with H-2 enabled us to obtain atomically resolved parameters relevant to their structural dynamics. While the presence of ras only marginally affected the packing of DMPC membranes, dramatically lower order parameters (S-CD) were observed for the ras acyl chains indicating modified packing properties. Essentially identical projected lengths of the 16:0 ras chains and the 14:0 DMPC chains were found, implying that the polypeptide backbone is located at the lipid-water interface. Dynamical properties of both the ras and phospholipid chains were determined from spin-lattice H-2 relaxation (R-1Z) measurements. Plots of R-1Z rates versus the corresponding squared segmental order parameters revealed striking differences. We propose the ras peptide is confined to microdomains containing DMPC chains which are in exchange with the bulk bilayer on the H-2 NMR time scale (similar to 10(-5)s). Compared to the host DMPC matrix, the ras lipid modifications are extremely flexible and undergo relatively large amplitude motions. It is hypothesized that this flexibility is a requirement for the optimal anchoring of lipid-modified proteins to cellular membranes.