FMOC-L-环丁基丙氨酸 | 478183-62-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: FMOC-L-环丁基丙氨酸
• 中文别名: FMOC-(BATA-环丁基)丙氨酸；Fmoc-L-环丁基丙氨酸；FMOC-Β-环丁基-L-丙氨酸
• 英文名称: (2S)-3-cyclobutyl-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)propanoic acid
• 英文别名: Fmoc-(β-cyclobutyl-Ala)-OH；Fmoc-L-cyclobutylalanine；Fmoc-ala(beta-cyclobutyl)-oh；(2S)-3-cyclobutyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 478183-62-9
• 化学式: C₂₂H₂₃NO₄
• 分子量: 365.429
• InChiKey: FOJRBUNCWCPLNH-FQEVSTJZSA-N

物化性质

• 沸点：
  592.2±33.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  29225090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  FMOC-L-环丁基丙氨酸 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (3S)-3-(((9H-fluoren-9-yl)methoxy)carbonylamino)-4-cyclobutyl-1-(cyclopropylamino)-1-oxobutan-2-yl acetate
  参考文献：
  名称：

  HCV INHIBITORS

  摘要：

  本发明涉及作为抗病毒剂的化合物。具体而言，本发明的化合物能抑制HCV的复制，因此在治疗丙型肝炎感染中非常有用。本发明还涉及包含这些化合物的药物组合物以及制备这些化合物的过程。

  公开号：

  US20080161254A1

文献信息

• Chemically Diverse Helix-Constrained Peptides Using Selenocysteine Crosslinking
  作者：Aline Dantas de Araujo、Samuel R. Perry、David P. Fairlie

  DOI：10.1021/acs.orglett.8b00233

  日期：2018.3.2

  The use of selenocysteines and various cross-linkers to induce helicity in a bioactive peptide is described. The higher reactivity of selenocysteine, relative to cysteine, facilitates rapid cross-linking within unprotected linear peptides under mild aqueous conditions. Alkylating agents of variable topology and electrophilicity were used to link pairs of selenocysteines within a p53 peptide. Facile

  描述了硒代半胱氨酸和各种交联剂在生物活性肽中诱导螺旋的用途。相对于半胱氨酸，硒代半胱氨酸的较高反应性促进了在温和的水性条件下未保护的线性肽内的快速交联。拓扑和亲电性可变的烷基化试剂用于连接p53肽中的半胱氨酸对。轻松的硒醚形成可实现螺旋肽结构的多种修饰。
• α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions
  作者：Peng Sang、Yan Shi、Junhao Lu、Lihong Chen、Leixiang Yang、Wade Borcherds、Sami Abdulkadir、Qi Li、Gary Daughdrill、Jiandong Chen、Jianfeng Cai

  DOI：10.1021/acs.jmedchem.9b00993

  日期：2020.2.13

  for the inhibition of protein-protein interactions (PPIs). Herein, we demonstrate that sulfono-γ-AApeptides can be rationally designed to mimic the p53 α-helix and inhibit p53-MDM2 PPIs. The best inhibitor, with Kd and IC50 values of 26 nM and 0.891 μM toward MDM2, respectively, is among the most potent unnatural peptidomimetic inhibitors disrupting the p53-MDM2/MDMX interaction. Using fluorescence polarization

  拟肽支架的使用是抑制蛋白相互作用的一种有前途的策略。在本文中，我们证明了可以合理设计磺基-γ-AA肽以模仿p53α-螺旋并抑制p53-MDM2 PPI。最好的抑制剂对MDM2的Kd和IC50值分别为26 nM和0.891μM，是破坏p53-MDM2 / MDMX相互作用的最有效的非天然拟肽抑制剂之一。使用荧光偏振分析，圆二色性，核磁共振波谱和计算模拟，我们证明了磺基-γ-AA肽采用类似于p53的螺旋结构，并通过结合到MDM2的疏水缝隙竞争性抑制p53-MDM2相互作用。有趣的是 通过增强p53转录活性并诱导MDM2和p21的表达，吻合的磺酰基-γ-AA肽显示出有希望的细胞活性。此外，磺基-γ-AA肽对蛋白水解表现出显着的抗性，从而增强了它们的生物学潜力。我们的结果表明，磺基-γ-AA肽是一类新型的破坏PPI的非天然螺旋折叠剂。
• Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein–Protein Interactions
  作者：Yan Shi、Peng Sang、Junhao Lu、Pirada Higbee、Lihong Chen、Leixiang Yang、Timothy Odom、Gary Daughdrill、Jiandong Chen、Jianfeng Cai

  DOI：10.1021/acs.jmedchem.0c01638

  日期：2020.11.12

  Peptidomimetics have gained great attention for their function as protein-protein interaction (PPI) inhibitors. Herein, we report the design and investigation of a series of right-handed helical heterogeneous 1:1 alpha/Sulfono-gamma-AA peptides as unprecedented inhibitors for p53-MDM2 and p53-MDMX. The most potent helical heterogeneous 1:1 alpha/Sulfono-gamma-AA peptides were shown to bind tightly to MDM2 and MDMX, with K-d of 19.3 and 66.8 nM, respectively. Circular dichroism spectra, 2D-NMR spectroscopy, and the computational simulations suggested that these helical sulfono-gamma-AA peptides could mimic the critical side chains of p53 and disrupt p53/MDM2 PPI effectively. It was noted that these 1:1 alpha/Sulfono-gamma-AA peptides were completely resistant to proteolytic degradation, boosting their potential for biomedical applications. Furthermore, effective cellular activity is achieved by the stapled 1:1 alpha/Sulfono-gamma-AA peptides, evidenced by significantly enhanced p53 transcriptional activity and much more induced level of MDM2 and p21. The 1:1 alpha/Sulfono-gamma-AA peptides could be an alternative strategy to antagonize a myriad of PPIs.
• Strategy for “Detoxification” of a Cancer-Derived Histone Mutant Based on Mapping Its Interaction with the Methyltransferase PRC2
  作者：Zachary Z. Brown、Manuel M. Müller、Siddhant U. Jain、C. David Allis、Peter W. Lewis、Tom W. Muir

  DOI：10.1021/ja5060934

  日期：2014.10.1

  The histone methyltransferase PRC2 plays a central role in genomic stability and cellular development. Consequently, its misregulation has been implicated in several cancers. Recent work has shown that a histone H3 mutant, where the PRC2 substrate residue Lys27 is replaced by methionine, is also associated with cancer phenotypes and functions as an inhibitor of PRC2. Here we investigate the mechanism of this PRC2 inhibition through kinetic studies and photo-cross-linking. Efficient inhibition is dependent on (1) hydrophobic lysine isosteres blocking the active site, (2) proximal residues, and (3) the H3 tail forming extensive contacts with the EZH2 subunit of PRC2. We further show that naturally occurring post-translational modifications of the same H3 tail, both proximal and distal to K27M, can greatly diminish the inhibition of PRC2. These results suggest that this potent gain of function mutation may be detoxified by modulating alternate chromatin modification pathways.
• Accelerated Identification of Cell Active KRAS Inhibitory Macrocyclic Peptides using Mixture Libraries and Automated Ligand Identification System (ALIS) Technology
  作者：Michael Garrigou、Bérengère Sauvagnat、Ruchia Duggal、Nicole Boo、Pooja Gopal、Jennifer M. Johnston、Anthony Partridge、Tomi Sawyer、Kaustav Biswas、Nicolas Boyer

  DOI：10.1021/acs.jmedchem.2c00154

  日期：2022.7.14