H-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe | 176664-79-2

• 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: H-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe
• 英文别名: Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe；methyl (2S)-2-[[(2S,3S)-2-[[2-[[2-[[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-4-methylpentanoyl]amino]-2-methylpropanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoate
• CAS: 176664-79-2
• 化学式: C₂₉H₅₃N₇O₈
• 分子量: 627.782
• InChiKey: DZLKJZVECFPLKR-XHOYROJHSA-N

物化性质

• 沸点：
  953.2±65.0 °C(Predicted)
• 密度：
  1.136±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  44.0
• 可旋转键数：
  19.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  226.92
• 氢给体数：
  7.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  H-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 生成 Cbz-Leu-Aib-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe
  参考文献：
  名称：

  Nα-酰基链长度对Lipopeptaibol Trichogin GA IV的合成类似物的膜改性特性的影响

  摘要：

  Trichogin GA IV 是一种在 N 端被正辛酰基封闭，在 C 端被 1,2-氨基醇（l-亮氨醇）封闭的 11 个残基脂肽醇，从真菌 Trichoderma longibrachiatum 中提取，表现出显着的效果膜改性特性。我们已经合成了 Trichogin GA IV 和几种 [l-Leu-OMe11] 类似物，在 N 端带有可变长度的酰基链（C2-C8、C10、C12、C14、C16、C18）。还制备了琥珀酰化的头对头二聚体。通过 FTIR 吸收、CD 和 NMR 进行的构象分析表明，天然 lipopeptaibol 的右手螺旋结构基本上保留在其所有类似物中。渗透性测量表明，Nα 阻断脂肪酰基部分中至少有六个碳原子是显着的膜改性特性的开始所必需的。此外，头对头二聚体非常活跃。讨论了 Trichogin GA IV 的膜通透性机制的可能模型。

  DOI：

  10.1021/ja954081o
• 作为产物：
  描述：

  L-Leucine, N-[(phenylmethoxy)carbonyl]-, anhydride with 2-methylpropyl hydrogen carbonate 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 生成 H-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe
  参考文献：
  名称：

  Nα-酰基链长度对Lipopeptaibol Trichogin GA IV的合成类似物的膜改性特性的影响

  摘要：

  Trichogin GA IV 是一种在 N 端被正辛酰基封闭，在 C 端被 1,2-氨基醇（l-亮氨醇）封闭的 11 个残基脂肽醇，从真菌 Trichoderma longibrachiatum 中提取，表现出显着的效果膜改性特性。我们已经合成了 Trichogin GA IV 和几种 [l-Leu-OMe11] 类似物，在 N 端带有可变长度的酰基链（C2-C8、C10、C12、C14、C16、C18）。还制备了琥珀酰化的头对头二聚体。通过 FTIR 吸收、CD 和 NMR 进行的构象分析表明，天然 lipopeptaibol 的右手螺旋结构基本上保留在其所有类似物中。渗透性测量表明，Nα 阻断脂肪酰基部分中至少有六个碳原子是显着的膜改性特性的开始所必需的。此外，头对头二聚体非常活跃。讨论了 Trichogin GA IV 的膜通透性机制的可能模型。

  DOI：

  10.1021/ja954081o

文献信息

• Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity
  作者：Marta De Zotti、Barbara Biondi、Cristina Peggion、Matteo De Poli、Haleh Fathi、Simona Oancea、Claudio Toniolo、Fernando Formaggio

  DOI：10.3762/bjoc.8.129

  日期：——

  common chemical tool to control the conformation of linear peptides and to explore potentially useful effects on their biochemical and biophysical properties. The thioamide, psi[CS-NH], group is a nearly isosteric structural mimic of the amide (peptide) functionality. In this paper, we describe the solution synthesis, chemical characterization, preferred conformation, and membrane and biological activities

  骨架修饰是一种常用的化学工具，用于控制线性肽的构象，并探索对其生化和生物物理特性的潜在有用影响。硫代酰胺 psi[CS-NH] 基团是酰胺（肽）功能的近等排结构模拟物。在本文中，我们描述了三种精心挑选的脂肽生物 [Leu(11)-OMe] 毛虫素 GA IV 的肽类似物的溶液合成、化学表征、优选构象以及膜和生物活性。在每个类似物中，加入了一个单一的硫代酰胺置换。研究了靠近 N 端、中心和靠近 C 端的序列位置。
• Trichogin GA IV: A versatile template for the synthesis of novel peptaibiotics
  作者：Marta De Zotti、Barbara Biondi、Cristina Peggion、Fernando Formaggio、Yoonkyung Park、Kyung-Soo Hahm、Claudio Toniolo

  DOI：10.1039/c1ob06178j

  日期：——

  Trichogin GA IV, isolated from the fungus Trichoderma longibrachiatum, is the prototype of lipopeptaibols, the sub-class of short-length peptaibiotics exhibiting membrane-modifying properties. This peptaibol is predominantly folded in a mixed 310-/α- helical conformation with a clear, albeit modest, amphiphilic character, which is likely to be responsible for its capability to perturb bacterial membranes and to induce cell death. In previous papers, we reported on the interesting biological properties of trichogin GA IV, namely its good activity against Gram positive bacteria, in particular methicillin-resistant S. aureus strains, its stability towards proteolytic degradation, and its low hemolytic activity. Aiming at broadening the antimicrobial activity spectrum by increasing the peptide helical amphiphilicity, in this work we synthesized, by solution and solid-phase methodologies, purified and fully characterized a set of trichogin GA IV analogs in which the four Gly residues at positions 2, 5, 6, 9, lying in the poorly hydrophilic face of the helical structure, are substituted by one (position 2, 5, 6 or 9), two (positions 5 and 6), three (positions 2, 5, and 9), and four (positions 2, 5, 6, and 9) Lys residues. The conformational preferences of the Lys-containing analogs were assessed by FT-IR absorption, CD and 2D-NMR techniques in aqueous, organic, and membrane-mimetic environments. Interestingly, it turns out that the presence of charged residues induces a transition of the helical conformation adopted by the peptaibols (from 310- to α-helix) as a function of pH in a reversible process. The role played in the analogs by the markedly increased amphiphilicity was further tested by fluorescence leakage experiments in model membranes, protease resistance, antibacterial and antifungal activities, cytotoxicity, and hemolysis. Taken together, our biological results provide evidence that some of the least substituted among these analogs are good candidates for the development of new membrane-active antimicrobial agents.

  从真菌长链毛霉中分离出来的 Trichogin GA IV 是具有膜修饰特性的短链肽亚类--脂链肽的原型。这种蛋白胨主要折叠成 310-/α- 混合螺旋构象，具有明显的两亲性，尽管这种两亲性并不强，但这很可能是它能够扰乱细菌膜并诱导细胞死亡的原因。在以前的论文中，我们曾报道过 trichogin GA IV 有趣的生物特性，即它对革兰氏阳性细菌（尤其是耐甲氧西林金黄色葡萄球菌菌株）的良好活性、对蛋白水解降解的稳定性以及较低的溶血活性。为了通过增加肽的螺旋两亲性来拓宽其抗菌活性谱，我们在这项工作中采用溶液法和固相法合成、纯化并充分表征了一组三叶草苷 GA IV 类似物、5、6、9 位的四个 Gly 残基被一个（2、5、6 或 9 位）、两个（5 和 6 位）、三个（2、5 和 9 位）和四个（2、5、6 和 9 位）Lys 残基取代。在水性、有机和膜模拟环境中，通过傅立叶变换红外吸收、CD 和二维核磁共振技术评估了含 Lys 类似物的构象偏好。有趣的是，事实证明，带电残基的存在会诱导七叶皂苷的螺旋构象（从 310 螺旋到 α 螺旋）随 pH 值的变化而发生转变，这是一个可逆的过程。通过在模型膜中的荧光泄漏实验、蛋白酶抗性、抗菌和抗真菌活性、细胞毒性和溶血作用，进一步检验了类似物显著增加的两亲性所发挥的作用。总之，我们的生物学结果证明，这些类似物中一些取代度最低的是开发新型膜活性抗菌剂的良好候选物。
• Short-chain analogues of the lipopeptaibol antibiotic trichogin GA IV: conformational analysis and membrane modifying properties
  作者：Fernando Formaggio、Cristina Peggion、Marco Crisma、Claudio Toniolo

  DOI：10.1039/b101373o

  日期：——

  To examine the role of the peptide main-chain length on the conformation and membrane activity of the lipopeptaibol antibiotic trichogin GA IV we have synthesized by solution methods the Leu11-OMe analogue and all its short, N-octanoylated C-terminal sequences. By FTIR absorption, 1H NMR and CD we have shown that largely folded, but not helical, forms characterize the short peptides, while the longest peptides predominantly adopt regular helical structures. Membrane activity is found in main-chain lengths as short as the tetrapeptide and progressively increases up to the undecapeptide.

  为了研究肽主链长度对脂多肽抗生素三肽GA IV的构象和膜活性的影响，我们采用溶液法合成了Leu11-OMe类似物及其所有短的N-辛酰化的C-末端序列。通过FTIR吸收、1H NMR和CD，我们发现短肽具有大折叠但无螺旋的特征，而最长肽则主要采用规则螺旋结构。我们发现膜活性存在于短至四肽的主链长度中，并逐渐增加到十一肽。
• Determining the occurrence of a 3 10 -helix and an α-helix in two different segments of a lipopeptaibol antibiotic using TOAC, a nitroxide spin-labeled C α -tetrasubstituted α-aminoacid
  作者：Vania Monaco、Fernando Formaggio、Marco Crisma、Claudio Toniolo、Paul Hanson、Glenn Millhauser、Clifford George、Jeffrey R. Deschamps、Judith L. Flippen-Anderson

  DOI：10.1016/s0968-0896(98)00220-x

  日期：1999.1

  Trichogin GA IV is a 11-residue lipopeptaibol antibiotic exhibiting membrane modifying properties. We synthesized step-by-step by solution methods three trichogin analogues, each with a double Aib (alpha-aminoisobutyric acid)-->TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) replacement. The strict similarity in the conformational propensities of Aib and TOAC allowed us to exploit these analogues in a detailed investigation of the conformation of this lipopeptaibol in different organic solvents and in a membrane-mimetic environment using in particular the double spin labeling ESR technique. We conclude that the secondary structure in solution remains essentially unchanged if compared to that previously found in the crystal state for trichogin. More specifically, the N-terminal region of the peptide folds in a 3(10)-helix, while the central and C-terminal regions are mainly alpha-helical. An additional, significant proof for the modest plasticity of the trichogin structure was obtained by an X-ray diffraction analysis of the nOct-[TOAC(4,8), Leu-OMe11] analogue. For the three analogues permeability measurements revealed membrane-modifying properties comparable to those of natural trichogin. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.