L-Leucyl-L-prolyl-(S-farnesyl)-L-cysteine methyl ester | 170892-91-8

• 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: L-Leucyl-L-prolyl-(S-farnesyl)-L-cysteine methyl ester
• 英文别名: HLeuProCys(Far)OMe；H-Leu-Pro-Cys((E,E)-farnesyl)-OMe；methyl (2R)-2-[[(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoate
• CAS: 170892-91-8
• 化学式: C₃₀H₅₁N₃O₄S
• 分子量: 549.819
• InChiKey: FREKPFLOUCMAQK-KSKXFUEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  38
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-Leucyl-L-prolyl-(S-farnesyl)-L-cysteine methyl ester 在 哌啶 、 1-羟基苯并三唑 、 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：

  Fmoc-Leu-Pro-OH 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 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 L-Leucyl-L-prolyl-(S-farnesyl)-L-cysteine methyl ester
  参考文献：
  名称：

  人N-Ras蛋白特征性脂肽的合成及其作为蛋白法呢基转移酶抑制剂的评估。

  摘要：

  带有法呢基硫醚或棕榈酸硫酯和法呢基硫醚的脂肽是通过使用钯（0）敏感的Aloc氨基甲酸酯的碱基不稳定的Fmoc封闭基团通过肽链的N端延伸从S-法呢基半胱氨酸甲酯制备的。通过该技术，制备了代表人N-Ras蛋白的完全官能化的，即棕榈酰化的和法尼基化的C末端的脂六肽。如果使用诸如Boc基团之类的对酸不稳定的阻断功能，则在脱保护时，会发生不希望的酸加到法呢基残基的双键上。因此，酸不稳定的保护基团不应用于合成法呢基脂肽。仅带有法呢基的脂肽甲酯不会抑制蛋白法呢基转移酶，

  DOI：

  10.1016/s0968-0896(96)00213-1

文献信息

• Chemoenzymatic Synthesis of N-<i>Ras</i> Lipopeptides
  作者：Edgar Nägele、Michael Schelhaas、Norman Kuder、Herbert Waldmann

  DOI：10.1021/ja9805627

  日期：1998.7.1

  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.
• 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：——
• Waldmann, Herbert; Naegele, Edgar, Angewandte Chemie, 1995, vol. 107, # 20, p. 2425 - 2428
  作者：Waldmann, Herbert、Naegele, Edgar

  DOI：——

  日期：——
• Schelhaas, Michael; Glomsda, Simone; Haensler, Marion, Angewandte Chemie, 1996, vol. 108, # 1, p. 82 - 85
  作者：Schelhaas, Michael、Glomsda, Simone、Haensler, Marion、Jakubke, Hans-Dieter、Waldmann, Herbert

  DOI：——

  日期：——
• Efficient Synthesis of a Fluorescent Farnesylated Ras Peptide
  作者：Zuping Xia、Charles D. Smith

  DOI：10.1021/jo015526w

  日期：2001.7.1