Fmoc-nleu-oh [Fmoc-n-(异丁基)-甘氨酸] | 141743-14-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: Fmoc-nleu-oh [Fmoc-n-(异丁基)-甘氨酸]
• 中文别名: Fmoc-nleu-oh[Fmoc-n-(异丁基)-甘氨酸]
• 英文名称: N-[(9H-fluoren-9-yl)methoxycarbonyl]-N-(isobutyl)glycine
• 英文别名: Glycine, N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-(2-methylpropyl)-；2-[9H-fluoren-9-ylmethoxycarbonyl(2-methylpropyl)amino]acetic acid
• CAS: 141743-14-8
• 化学式: C₂₁H₂₃NO₄
• mdl: MFCD18351999
• 分子量: 353.418
• InChiKey: AEQVNDSKGYFDSR-UHFFFAOYSA-N

物化性质

• 沸点：
  533.1±29.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  Fmoc-nleu-oh [Fmoc-n-(异丁基)-甘氨酸] 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  内酰胺连续扩环合成环肽模拟物

  摘要：

  据报道，有连续的扩环方案可以将天然和非天然氨基酸片段控制插入内酰胺中。可以通过操作简单且可扩展的迭代程序将氨基酸安装到大环化合物中，而无需进行高稀释。预期该方法具有广泛的用途，特别是对于合成具有医学重要性的环状肽模拟物而言。

  DOI：

  10.1002/chem.201703316
• 作为产物：
  描述：

  N-异丁基甘氨酸乙酯 在 盐酸 、 sodium hydroxide 、 TEA 、 水 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 1.0h， 生成 Fmoc-nleu-oh [Fmoc-n-(异丁基)-甘氨酸]
  参考文献：
  名称：

  Solid-Phase Syntheses of Peptoids using Fmoc-ProtectedN-Substituted Glycines: The Synthesis of (Retro)Peptoids of Leu-Enkephalin and Substance P

  摘要：

  A particularly interesting class of oligomeric peptidomimetics is formed by the peptoids, which consist of N-substituted glycine residues. A solid-phase synthesis method for peptoids is presented in which these residues are introduced using their Fmoc derivatives. This "monomer" method allowed the monitored synthesis of relatively large quantities of pure peptoids as well as the translation of, in principle, any peptide into the corresponding peptoid. The required Fmoc-substituted glycines were accessible by convenient synthesis, and a number of monomers including those containing side chains with functional groups have been synthesized. The use of Fmoc monomers also allowed implementation of a solid-phase synthesis protocol on a commercial peptide synthesizer. The method was exemplified by the solid-phase syntheses of the (retro)peptoids of Leu-enkephalin and substance P. Mass spectrometric studies of (retro)peptoids were essential for their characterization, and the presence of the B- and Y "- type ions allows sequence analysis. Substance P (retro)-peptoids were biologically active. HPLC analysis showed an increased hydrophobicity, and pepsin treatment resulted in greatly reduced degradation compared with the corresponding peptide.

  DOI：

  10.1002/(sici)1521-3765(19980807)4:8<1570::aid-chem1570>3.0.co;2-2

文献信息

• Effect of Double Replacement of L-Pro, D-Pro, D-Leu or Nleu in Hydrophobic Face of Amphipathic α-Helical Model Antimicrobial Peptide on Structure, Cell Selectivity and Mechanism of Action
  作者：Song Yub Shin

  DOI：10.5012/bkcs.2014.35.11.3267

  日期：2014.11.20

  In order to investigate the effects of the double replacement of $\smallL}$-Pro, $\smallD}$-Pro, $\smallD}$-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic $\alpha}$-helical non-cell-selective antimicrobial peptide $L_8K_9W_1$ on the structure, cell selectivity and mechanism of action, we synthesized a series of $L_8K_9W_1$ analogs with double replacement of $\smallL}$-Pro, $\smallD}$-Pro, $\smallD}$-Leu or Nleu in the hydrophobic face of $L_8K_9W_1$. In this study, we have confirmed that the double replacement of $\smallL}$-Pro, $\smallD}$-Pro, or Nleu in the hydrophobic face of $L_8K_9W_1$ let to a great increase in the selectivity toward bacterial cells and a complete destruction of $\alpha}$-helical structure. Interestingly, $L_8K_9W_1$-$\smallL}$-Pro, $L_8K_9W_1$-$\smallD}$-Pro and $L_8K_9W_1$-Nleu preferentially interacted with negatively charged phospholipids, but unlike $L_8K_9W_1$ and $L_8K_9W_1$-$\smallD}$-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of $L_8K_9W_1$-$\smallL}$-Pro, $L_8K_9W_1$-$\smallD}$-Pro and $L_8K_9W_1$-Nleu involves the intracellular target other than the bacterial membrane. In particular, $L_8K_9W_1$-$\smallL}$-Pro, $L_8K_9W_1$-$\smallD}$-Pro and $L_8K_9W_1$-Nleu had powerful antimicrobial activity (MIC range, 1 to $4\mu}M$) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that $L_8K_9W_1$-$\smallL}$-Pro, $L_8K_9W_1$-$\smallD}$-Pro and $L_8K_9W_1$-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.

  为了研究在亲水性$\alpha}$螺旋非细胞选择性抗菌肽$L_8K_9W_1$的疏水面（位置9和13）上进行的双重替换，即$\smallL}$-Pro、$\smallD}$-Pro、$\smallD}$-Leu或Nleu（Leu的肽类似物残基）对结构、细胞选择性和作用机制的影响，我们合成了一系列在$L_8K_9W_1$的疏水面上进行$\smallL}$-Pro、$\smallD}$-Pro、$\smallD}$-Leu或Nleu双重替换的$L_8K_9W_1$类似物。在本研究中，我们已经证实，在$L_8K_9W_1$的疏水面上进行$\smallL}$-Pro、$\smallD}$-Pro或Nleu的双重替换导致了对细菌细胞的选择性显著增加，并完全破坏了$\alpha}$螺旋结构。有趣的是，$L_8K_9W_1$-$\smallL}$-Pro、$L_8K_9W_1$-$\smallD}$-Pro和$L_8K_9W_1$-Nleu优先与带负电的磷脂相互作用，但与$L_8K_9W_1$和$L_8K_9W_1$-$\smallD}$-Leu不同，它们没有破坏脂质双层的完整性并去极化细菌细胞质膜。这些结果表明，$L_8K_9W_1$-$\smallL}$-Pro、$L_8K_9W_1$-$\smallD}$-Pro和$L_8K_9W_1$-Nleu的作用机制涉及细菌膜以外的细胞内靶点。特别是，$L_8K_9W_1$-$\smallL}$-Pro、$L_8K_9W_1$-$\smallD}$-Pro和$L_8K_9W_1$-Nleu对耐甲氧西林金黄色葡萄球菌（MRSA）和多药耐药铜绿假单胞菌（MDRPA）具有强大的抗菌活性（MIC范围为1至$4\mu}M$）。综上所述，我们的结果表明，具有高细胞选择性的$L_8K_9W_1$-$\smallL}$-Pro、$L_8K_9W_1$-$\smallD}$-Pro和$L_8K_9W_1$-Nleu可能是新疗法的有希望的候选者，补充传统抗生素疗法以对抗病原微生物。
• Sequencing of peptoid peptidomimetics by Edman degradation
  作者：Astrid Boeijen、Rob M.J. Liskamp

  DOI：10.1016/s0040-4039(98)00556-5

  日期：1998.5

  The direct identification of resin-bound peptoid peptidomimetics by sequencing is described. The N-terminus of the peptoid was treated with phenyl isothiocyanate, after which the N-terminal peptoid residue was cleaved from the resin as its thiohydantoin derivative. For deduction of the peptoid sequence, the HPLC retention times of the obtained thiohydantoins were compared to those of independently

  描述了通过测序直接鉴定树脂结合的类肽拟肽。用异硫氰酸苯酯处理拟肽的N-末端，然后从树脂上裂解N-末端拟肽残基作为其硫代乙内酰脲衍生物。为了推导类肽序列，将获得的巯基乙内酰脲的HPLC保留时间与独立制备的参考巯基乙内酰脲的HPLC保留时间进行了比较。
• Apoptotic compounds
  申请人：Board of Regents, The university of Texas System

  公开号：US20040077542A1

  公开（公告）日：2004-04-22

  The invention provides methods and compositions for enhancing apoptosis of pathogenic cells. The general method comprises the of contacting the cells with an effective amount of an AV peptoid, wherein the AV peptoid is a peptide comprising AX 1 , wherein X 1 is V, I or L, or a peptide mimetic thereof, which interacts with an Inhibitor of Apoptosis protein (IAP) as measured by IAP binding, procaspase-3 activation or promotion of apoptosis, wherein apoptosis of the pathogenic cells is enhanced. The subject compositions encompass pharmaceutical compositions comprising a therapeutically effective amount of a subject AV peptoid in dosage form and a pharmaceutically acceptable carrier, wherein the AV peptoid is a peptide comprising AX 1 , wherein X 1 is V, I or L, or a peptide mimetic thereof, which inhibits the activity of an Inhibitor of Apoptosis protein (IAP) as measured by IAP binding, procaspase-3 activation or promotion of apoptosis. The invention also provides assays for identifying agents which modulates the interaction of an AV peptoid with an IAP, active compounds identified in such screens and their use in the foregoing compositions and therapeutic methods.

  本发明提供了增强致病细胞凋亡的方法和组合物。一般方法包括将细胞与有效量的AV肽类接触，其中AV肽类是包含AX1的肽类，其中X1为V、I或L，或其肽类类似物，通过IAP结合、procaspase-3激活或促进凋亡等测量方式与凋亡抑制蛋白（IAP）相互作用，从而增强致病细胞的凋亡。所述组合物包括在制剂中含有治疗有效量的AV肽类和药学可接受的载体的制药组合物，其中AV肽类是包含AX1的肽类，其中X1为V、I或L，或其肽类类似物，通过IAP结合、procaspase-3激活或促进凋亡等测量方式抑制凋亡抑制蛋白（IAP）的活性。本发明还提供了用于识别调节AV肽类与IAP相互作用的试剂的测定方法，以及在此类筛选中鉴定出的活性化合物及其在上述组合物和治疗方法中的应用。
• Peptoid mixtures
  申请人：Chiron Corporation

  公开号：US05811387A1

  公开（公告）日：1998-09-22

  Mixtures of peptoids are provided. The subject peptoid mixtures comprise at least five non-homopolymeric polymers of differing sequences having a selected number of monomer units. The polymers of the subject mixtures are preferably selected from the group of compounds of the general formula: X.sub.a --(NR--CH.sub.2 --CO).sub.n --X.sub.b, X.sub.a --(O--CHR--CO).sub.n --X.sub.b, X.sub.a --(NH--CHR--CS).sub.n --X.sub.b, X.sub.a --(NOH--CHR--CO).sub.n --X.sub.b, X.sub.a --(O--CHR--CH.sub.2 --CO).sub.n --X.sub.b, X.sub.a --(NH--CHR--CH.sub.2 --SO.sub.2).sub.n --Xb, Xa--(NR--CH.sub.2 CH.sub.2 --SO.sub.2).sub.n --X.sub.b, X.sub.a --(NR--CH.sub.2 CH.sub.2 --NHCO).sub.n --X.sub.b and X.sub.a --(NR--CH.sub.2 CH.sub.2 --OCO).sub.n X.sub.b, where each R is independently a side chain capable of interaction with a protein, carbohydrate, lipid or nucleic acid; n is an integer from 2 to 50, inclusive; and X.sub.a and X.sub.b are each independently H, lower alkyl, lower aryl, aralkyl, lower acyl, a polypeptide of 1-100 amino acids, or an effector molecule capable of exhibiting biological activity.

  本发明提供了肽酰胺混合物。所述肽酰胺混合物包括至少五种不同序列的非同质聚合物，具有选定数量的单体单位。所述混合物中的聚合物优选从以下化合物组中选择：X.sub.a --(NR--CH.sub.2 --CO).sub.n --X.sub.b、X.sub.a --(O--CHR--CO).sub.n --X.sub.b、X.sub.a --(NH--CHR--CS).sub.n --X.sub.b、X.sub.a --(NOH--CHR--CO).sub.n --X.sub.b、X.sub.a --(O--CHR--CH.sub.2 --CO).sub.n --X.sub.b、X.sub.a --(NH--CHR--CH.sub.2 --SO.sub.2).sub.n --Xb、Xa--(NR--CH.sub.2 CH.sub.2 --SO.sub.2).sub.n --X.sub.b、X.sub.a --(NR--CH.sub.2 CH.sub.2 --NHCO).sub.n --X.sub.b 和 X.sub.a --(NR--CH.sub.2 CH.sub.2 --OCO).sub.n X.sub.b，其中每个R独立地是能够与蛋白质、碳水化合物、脂质或核酸相互作用的侧链；n是2到50之间的整数，包括2和50；X.sub.a和X.sub.b各自独立地是H、低烷基、低芳基、aryl基、低酰基、1-100个氨基酸的多肽或能够表现生物活性的效应分子。
• Modified peptide and peptide libraries with protease resistance,
  申请人：Chiron Corporation

  公开号：US06075121A1

  公开（公告）日：2000-06-13

  Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include at least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Although the peptoids may include amino acids, they preferably include only substituted amino acids and are designed in a manner so as to have a particular biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. In that the peptoids are comprised of substitute amino acids they can be designed to have structures which natural proteins cannot conform to. A range of different amino acid substitutes are disclosed, as are their methods of synthesis and methods of using such amino acid substitutes in the synthesis of peptoids and peptoid libraries. Methods of screening the libraries in order to obtain desired peptoids of a particular biological activity are also disclosed. The peptoids are preferably linked to a pharmaceutically active drug forming a conjugate with increased binding affinity to a particular biological receptor site.

  提供了一种聚合物Peptoids，由单体单元组成，其中单体单元包括至少一些替代氨基酸，也可以包括传统的氨基酸。Peptoids可以大量合成，以提供Peptoids库，可以筛选以分离所需生物活性的Peptoids。虽然Peptoids可能包含氨基酸，但最好仅包含替代氨基酸，并以一种设计方式设计，以具有特定的生物活性。某些Peptoids被设计成尽可能接近已知蛋白质的活性。其他Peptoids被设计为具有比已知蛋白质更大或更小的活性，并可以设计为阻止已知的受体位点和/或引发所需的免疫反应，从而作为疫苗。由于Peptoids由替代氨基酸组成，因此它们可以被设计成具有自然蛋白质无法符合的结构。公开了一系列不同的氨基酸替代物，以及它们的合成方法和在Peptoids和Peptoids库的合成中使用这些氨基酸替代物的方法。还公开了筛选库以获得特定生物活性的所需Peptoids的方法。Peptoids最好与药物结合形成药物共轭物，具有增强对特定生物受体位点的结合亲和力。