benzyl 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentyl]amino]acetate | 1287745-39-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: benzyl 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentyl]amino]acetate
• CAS: 1287745-39-4
• 化学式: C₃₀H₃₄N₂O₄
• 分子量: 486.611
• InChiKey: DXKTXNDTLCGGHM-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentyl]amino]acetate 在 palladium 10% on activated carbon 、 氢气 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-N-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-methylpentyl)-N-(4-methylpentanoyl)glycine
  参考文献：
  名称：

  γ-AApeptides: design, synthesis and evaluation

  摘要：

  一种新型肽类似物被称为“γ-AA肽”，已被描述。γ-AA肽的设计和合成，以及其对p53/MDM2相互作用的潜在生物活性得到了证明。研究还发现，γ-AA肽对蛋白酶降解具有高度抗性。开发特定序列的γ-AA肽可能会引领一系列具有新框架的肽类模拟物，有助于药物发现或肽/蛋白的模仿。

  DOI：

  10.1039/c0nj00943a
• 作为产物：
  描述：

  (S)-(9H-fluoren-9-yl)methyl (1-(methoxy(methyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate 在 lithium aluminium tetrahydride 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.42h， 生成 benzyl 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentyl]amino]acetate
  参考文献：
  名称：

  具有增强稳定性和延长体内活性的胰高血糖素 α/磺基-γ-A肽混合类似物

  摘要：

  多肽药物具有靶点特异性、成药性好等优点，已成为生物医学领域新药研究日益重要的热点之一。然而，肽药物普遍生物利用度和代谢稳定性较低，因此，对现有肽药物进行修饰以提高稳定性和保留活性具有重要意义。众所周知，胰高血糖素是治疗严重低血糖的有效疗法，但其半衰期短阻碍了其广泛的治疗用途。在此，我们报道，组合的非天然残基和长脂肪酸缀合提供了有效的胰高血糖素α/磺基-γ-A肽混合类似物，具有增强的稳定性和延长的体内活性。该策略可用于开发其他短效生物活性肽的稳定类似物。

  DOI：

  10.1021/acs.jmedchem.1c01289

文献信息

• GAMMA-AAPEPTIDES WITH POTENT AND BROAD-SPECTRUM ANTIMICROBIAL ACTIVITY
  申请人：Cai Jianfeng

  公开号：US20150274782A1

  公开（公告）日：2015-10-01

  The present invention is directed to a novel class of antimicrobial agents called γ-AApeptides. The current invention provides various categories of γ-AApeptides, for example, linear γ-AApeptides, cyclic γ-AApeptides, and lipidated γ-AApeptides. γ-AApeptides of the current invention are designed to exert antimicrobial activity while being stable and non-toxic. γ-AApeptides also do not appear to lead to the development of microbial resistance in treated microorganisms. Thus, the disclosed γ-AApeptides can be used for the treatment of various medical conditions associated with pathogenic microorganisms.

  本发明涉及一种新型类别的抗微生物药物，称为γ-AA肽。当前发明提供了各种类别的γ-AA肽，例如线性γ-AA肽、环状γ-AA肽和脂质化γ-AA肽。本发明的γ-AA肽被设计为具有抗微生物活性，同时稳定且无毒。γ-AA肽似乎也不会导致被治疗微生物体内微生物产生抗药性。因此，所披露的γ-AA肽可用于治疗与病原微生物相关的各种医疗状况。
• Lipo-γ-AApeptides as a New Class of Potent and Broad-Spectrum Antimicrobial Agents
  作者：Youhong Niu、Shruti Padhee、Haifan Wu、Ge Bai、Qiao Qiao、Yaogang Hu、Lacey Harrington、Whittney N. Burda、Lindsey N. Shaw、Chuanhai Cao、Jianfeng Cai

  DOI：10.1021/jm300274p

  日期：2012.4.26

  antibiotic agents, as they have the potential to circumvent emerging drug resistance against conventional antibiotic treatments. Non-natural antimicrobial peptidomimetics are an ideal example of this, as they have significant potency and in vivo stability. Here we report for the first time the design of lipidated γ-AApeptides as antimicrobial agents. These lipo-γ-AApeptides show potent broad-spectrum activities

  对开发抗菌肽（AMPs）作为下一代抗生素的需求日益增长，因为它们具有规避新兴的对常规抗生素治疗的耐药性的潜力。非天然抗菌肽模拟物是一个理想的例子，因为它们具有显着的效力和体内稳定性。在这里，我们首次报道了脂化的γ-AA肽作为抗菌剂的设计。这些脂质-γ-AA肽对真菌和一系列革兰氏阳性和革兰氏阴性细菌（包括对大多数抗生素具有抗药性的临床相关病原体）显示出有效的广谱活性。我们使用膜去极化和荧光显微镜分析了它们的结构-功能关系和抗菌机制。引入不饱和脂质链显着降低了溶血活性，从而提高了选择性。此外，代表性的lipo-γ-AA肽不会在小鼠体内诱导耐药性金黄色葡萄球菌，即使经过17轮传代。这些结果表明，脂质-γ-AA肽具有类似于AMP的杀菌机制，并且具有作为新型新型抗生素治疗剂的强大潜力。
• Identification of γ-AApeptides with potent and broad-spectrum antimicrobial activity
  作者：Youhong Niu、Shruti Padhee、Haifan Wu、Ge Bai、Lacey Harrington、Whittney N. Burda、Lindsey N. Shaw、Chuanhai Cao、Jianfeng Cai

  DOI：10.1039/c1cc14476f

  日期：——

  We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance.

  我们报告发现了一类新的抗菌肽拟物类--δ-A肽，它们具有强效、广谱的活性，包括对大多数抗生素无反应的临床相关菌株。它们也不易产生耐药性。
• DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes
  作者：Ralph E. Kleiner、Yevgeny Brudno、Michael E. Birnbaum、David R. Liu

  DOI：10.1021/ja0753997

  日期：2008.4.1

  The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step toward the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities.
• US9499587B2
  申请人：——

  公开号：US9499587B2

  公开（公告）日：2016-11-22