FMOC-4,5-脱氢-Leu-OH | 87720-55-6

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: FMOC-4,5-脱氢-Leu-OH
• 中文别名: FMOC-(S)-甲基烯丙基甘氨酸
• 英文名称: N-fluoren-9-ylmethyloxycarbonyl-4,5-dehydro-L-leucine
• 英文别名: Fmoc-4,5-dehydro-l-leucine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpent-4-enoic acid
• CAS: 87720-55-6
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: YUPPKUMKKSBZRL-IBGZPJMESA-N

物化性质

• 沸点：
  569.8±45.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  29225090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  FMOC-4,5-脱氢-Leu-OH 在 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 (S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-(2-methyl-oxiranyl)-propionic acid methyl ester
  参考文献：
  名称：

  Irreversible Inhibition of the HIV-1 Protease:  Targeting Alkylating Agents to the Catalytic Aspartate Groups

  摘要：

  Irreversible inhibition of the HIV-1 protease by agents that specifically alkylate its catalytic aspartate residues is a potentially useful approach for circumventing the evolution of HIV strains that are resistant to protease inhibitors. Five haloperidol- and two FMOC-based epoxides of differing reactivities have been synthesized and tested as irreversible inhibitors of the HIV-1 protease (HIV-1 PR). Of these, two trisubstituted epoxides, a cis-1,2- disubstituted epoxide, a 1,1-disubstituted epoxide, and a monosubstituted epoxide function as irreversible inhibitors, but two trans-1,2-disubstituted epoxides do not. The most effective of the epoxides (6) inactivates HIV-1 PR with K-inact = 65 mu M and V-inact = 0.009 min(-1). 1,2-Epoxy-3-(p-nitrophenoxy)propane (EPNP), a nonspecific inactivating agent for aspartyl proteases, has been used to validate a protocol for establishing the stoichiometry and site of protein alkylation. Mass spectrometric analysis of the inactivated enzyme shows that one molecule of either EPNP or the cyclic 1,2-disubstituted epoxide 6 is covalently bound per HIV-1 PR dimer. Mass spectrometric sequencing of labeled proteolytic peptides shows that both inhibitors are covalently bound to a catalytic aspartate residue. The covalent binding of three alpha,beta-unsaturated ketone derivatives of haloperidol has been similarly examined. Analysis of HIV-1 PR inactivated by these agents establishes that they bind covalently to the two cysteines and the N-terminal amino group but not detectably to the catalytic aspartate residues. The results indicate that aspartate-targeted inactivation of HIV-1 PR depends on (a) matching the reactivity of the alkylating functionality to that of the aspartates, preferably by exploiting the two-aspartate catalytic motif of the protease to activate the alkylating agent, and (b) appropriate positioning of the alkylating functionality within the active site. These requirements are readily met by a monosubstituted, 1,1-disubstituted, or cyclic cis-1,2-disubstituted epoxide but not by trans-1,2-disubstituted epoxides or alpha,beta-unsaturated ketones.

  DOI：

  10.1021/ja954069w
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 4,5-脱氢亮氨酸 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以90%的产率得到FMOC-4,5-脱氢-Leu-OH
  参考文献：
  名称：

  [4,5-dehydroLeu 2 ]-和[3,4- dehydropro 6 ]-蝗虫脂肪动力学激素的合成

  摘要：

  通过固相法制备的N末端六肽与常见的C末端四肽的偶联，合成[4,5-dehydroLeu 2 ]-和[3,4-dehydroPro 6 ]-蝗脂肪动力学激素（LAKH）。描述了在溶液中合成。在剂量为20 pmol时，前者的生物活性至少与LAKH相同，而后者仅约20mg 。活动的20％。讨论了在将4，5-脱氢亮氨酸残基掺入肽中遇到的困难。

  DOI：

  10.1039/p19830000723

文献信息

• Synthesis and Anti-Helicobacter pylori Activity of Pyloricidin Derivatives. I. Structure-activity Relationships on the Terminal Peptidic Moiety.
  作者：ATSUSHI HASUOKA、YUJI NISHIKIMI、YUTAKA NAKAYAMA、KEIJI KAMIYAMA、MASAFUMI NAKAO、KEN-ICHIRO MIYAGAWA、OSAMU NISHIMURA、MASAHIKO FUJINO

  DOI：10.7164/antibiotics.55.322

  日期：——

  The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori. In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H. pylori activity. The derivatives bearing α-D-, β- and γ-amino acids or peptidemimetics showed drastically decreased activity. On the other hand, the derivatives with α-L-amino acids were found to maintain the activity. Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H. pylori activity, with an MIC value of less than 0.006μg/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.

  新型天然抗生素喷菌素A、B和C对幽门螺杆菌具有强效且高度选择性的抗菌活性。为了研究末端肽部分的结构-活性关系，制备了一系列含不同氨基酸的喷菌素B和喷菌素C衍生物，并评估了它们的抗幽门螺杆菌活性。含有α-D-、β-和γ-氨基酸或肽模拟物的衍生物显示出显著降低的活性。另一方面，含有α-L-氨基酸的衍生物被发现能保持活性。在本工作中制备的衍生物中，烯丙基甘氨酸衍生物2s表现出最强的抗幽门螺杆菌活性，对幽门螺杆菌NCTC11637的最低抑制浓度（MIC）值小于0.006μg/ml，比原始化合物喷菌素C的活性高出60倍。
• Exploration of the fifth position of leu-enkephalin and its role in binding and activating delta (DOP) and mu (MOP) opioid receptors
  作者：Dominique Bella Ndong、Véronique Blais、Brian J. Holleran、Arnaud Proteau-Gagné、Isabelle Cantin-Savoie、William Robert、Jean-François Nadon、Sophie Beauchemin、Richard Leduc、Graciela Piñeyro、Brigitte Guérin、Louis Gendron、Yves L. Dory

  DOI：10.1002/pep2.24070

  日期：2019.1

  receptors. We found that replacement of the leucine residue by substituted non‐natural amino acid derivatives of alanine, cycloleucine, or isoleucine was generally well tolerated. By contrast, substituting leucine with homoproline greatly reduced the affinity for DOP and, to a lesser extent, for MOP. Interestingly, when compared to Leu‐enkephalin, analogs containing either aza‐β‐homoleucine or cycloleucine

  脑啡肽是五肽内源性配体，通过与mu（MOP）和delta（DOP）阿片受体结合来调节伤害感受。为了进一步探索亮氨酸脑啡肽亮氨酸残基的作用，通过用非天然氨基酸系统取代该残基，合成了12种拟肽类似物。测试类似物结合DOP和MOP的能力。我们还研究了这些类似物抑制cAMP产生并通过两个受体募集β-arrestin2的能力。我们发现，丙氨酸，环亮氨酸或异亮氨酸的取代非天然氨基酸衍生物替代亮氨酸残基通常具有良好的耐受性。相比之下，用高脯氨酸取代亮氨酸大大降低了对DOP的亲和力，并在较小程度上降低了对MOP的亲和力。有趣的是，与亮脑啡肽相比，含有氮杂-β-高亮氨酸或环亮氨酸的类似物表现出倾向于通过激活DOP而不是MOP抑制cAMP的产生。相反，含有4,5-脱氢亮氨酸或d -allo-isoleucine在MOP时偏向β-arrestin2，而在DOP时偏向。我们的结果表明，亮脑啡肽类似物中的位置5可以
• Total Synthesis of the Death Cap Toxin Phalloidin: Atropoisomer Selectivity Explained by Molecular‐Dynamics Simulations
  作者：Guiyang Yao、Jan‐Oliver Joswig、Bettina G. Keller、Roderich D. Süssmuth

  DOI：10.1002/chem.201901888

  日期：2019.6.18

  and in a fluorescently labeled form widely used as a probe for actin binding. Herein, we report the enantioselective synthesis of the key amino acid (2S,4R)‐4,5‐dihydroxy‐leucine as a basis for the first total synthesis of phalloidin, which was accomplished by two different synthesis strategies. Molecular‐dynamics simulations provided insights into the conformational flexibility of peptide intermediates

  鬼伞毒素和Amatoxins是由死顶蘑菇伞形毒蕈产生的一组突出的肽毒素。鬼笔环肽是一种双环环肽，具有不寻常的类胰肽硫醚硫醚桥。它是一种有效的丝状肌动蛋白稳定剂，具有荧光标记的形式，广泛用作肌动蛋白结合的探针。在这里，我们报告关键氨基酸（2 S，4 R）‐4,5-二羟基亮氨酸作为首次完全合成鬼笔环肽的基础，这是通过两种不同的合成策略完成的。分子动力学模拟提供了对不同反应策略的肽中间体构象柔性的见解，并表明该柔性对于阻转异构体的形成至关重要。通过模拟中间体而不是最终产物，分子动力学模拟将成为协调复杂环肽成环反应顺序的决定性工具。
• Direct incorporation of unprotected ketone groups into peptides during solid-phase synthesis: Application to the one-step modification of peptides with two different biophysical probes for FRET
  作者：Lisa A. Marcaurelle、Carolyn R. Bertozzi

  DOI：10.1016/s0040-4039(98)01588-3

  日期：1998.10

  An amino acid bearing an unprotected ketone group, (2S)-aminolevulinic acid, was incorporated into a synthetic peptide using standard Fmoc-based solid-phase methods. The ketone group remained unharmed during the synthesis and provided a uniquely reactive functional group for covalent modification of the peptide. The ketone and the sulfhydryl group of a cysteine residue elsewhere in the peptide were

  使用标准的基于Fmoc的固相方法将带有未保护的酮基的氨基酸（2S）-氨基乙酰丙酸掺入合成肽中。酮基在合成过程中保持不受损害，并为肽的共价修饰提供了独特的反应性官能团。使肽中其他位置的半胱氨酸残基的酮和巯基与两种不同的生物物理探针同时反应，从而能够在一个步骤中针对FRET供体和受体对进行位点特异性安装，而无需进行差分侧链保护。
• Structure–activity relationship studies of permeability modulating peptide AT-1002
  作者：Min Li、Ed Oliver、Kelly M. Kitchens、John Vere、Sefik S. Alkan、Amir P. Tamiz

  DOI：10.1016/j.bmcl.2008.07.028

  日期：2008.8

  AT-1002 a 6-mer synthetic peptide belongs to an emerging novel class of compounds that reversibly increase paracellular transport of molecules across the epithelial barrier. The aim of this project was to elaborate on the structure-activity relationship of this peptide with the specific goal to replace the P2 cysteine amino acid. Herein, we report the discovery of peptides that exhibit reversible permeability enhancement properties with an increased stability profile. (C) 2008 Elsevier Ltd. All rights reserved.