Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys(farnesyl) | 212119-84-1

• 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: Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys(farnesyl)
• 英文别名: H-Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys((E,E)-farnesyl)-OMe；methyl (2R)-2-[[(2S)-1-[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-hexadecanoylsulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]acetyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoate
• CAS: 212119-84-1
• 化学式: C₅₈H₁₀₁N₇O₉S₃
• 分子量: 1136.68
• InChiKey: KUOCCAINPWRHTQ-FGHFRIAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  77
• 可旋转键数：
  45
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  311
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys(farnesyl) 、 3-氟硼吡咯-丙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene)-Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys(farnesyl)-OMe
  参考文献：
  名称：

  Partitioning of Dual-Lipidated Peptides into Membrane Microdomains:  Lipid Sorting vs Peptide Aggregation

  摘要：

  The lateral membrane organization and phase behavior of the lipid mixture DMPC(di-C-14)/DSPC(di-C-18)/cholesterol (0-33 mol %) with and without an incorporated fluorescence-labeled palmitoyl/farnesyl dual-lipidated peptide, BODIPY-Gly-Cys(Pal)-Met-Gly-Leu-Pro-Cys(Far)-OMe, which represents a membrane recognition model system for Ras proteins, was studied by two-photon excitation fluorescence microscopy. Measurements were performed on giant unilamellar vesicles (GUVs) over a large temperature range, ranging from 30 to 80 degreesC to cover different lipid phase states (all-gel, fluid/gel, liquid-ordered, all-fluid). At temperatures where the fluid-gel coexistence region of the pure binary phospholipid system occurs, large-scale concentration fluctuations appear. Incorporation of cholesterol levels up to 33 mol % leads to a significant increase of conformational order in the membrane system and a reduction of large domain structures. Adding the peptide leads to dramatic changes in the lateral organization of the membrane. With cholesterol present, a phase separation is induced by a lipid sorting mechanism owing to the high affinity of the lipidated peptide to a fluid, DMPC-rich environment. This phase separation leads to the formation of peptide-containing domains with high fluorescence intensity that become progressively smaller with decreasing temperature. As a result, the local concentration of the peptide increases steadily within the confines of the shrinking domains. At the lowest temperatures, where the acyl-chain order parameter of the membrane has already drastically increased and the membrane achieves a liquid-ordered character, an efficient lipid sorting mechanism is no longer supported and aggregation of the peptide into small clusters prevails. We can conclude that palmitoyl/farnesyl dual-lipidated peptides do not associate with liquid-ordered or gel-like domains in phase-separated bilayer membranes. In particular, the study shows the interesting ability of the peptide to induce formation of fluid microdomains at physiologically relevant cholesterol concentrations, and this effect very much depends on the concentration of fluid vs ordered lipid molecules.

  DOI：

  10.1021/ja049922i
• 作为产物：
  描述：

  2-[[(2S)-2-[(4-acetyloxyphenyl)methoxycarbonylamino]-4-methylsulfanylbutanoyl]amino]acetic acid 在 acetyl esterase 、 lipase from Mucor miehei 、 phosphate buffer pH=6 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 potassium iodide 、 dimethyl-β-cyclodextrin 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 Gly-Cys(palmitoyl)-Met-Gly-Leu-Pro-Cys(farnesyl)
  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