L-ornithinamide | 74718-02-8

• 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: L-ornithinamide
• 英文别名: Ornithinamide, L-；(2S)-2,5-diaminopentanamide
• CAS: 74718-02-8
• 化学式: C₅H₁₃N₃O
• 分子量: 131.178
• InChiKey: OERRZAJTKPMGBB-BYPYZUCNSA-N

物化性质

• 沸点：
  349.9±32.0 °C(Predicted)
• 密度：
  1.096±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  95.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-ornithinamide 、 万古霉素 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Vancomycin–Arginine Conjugate Inhibits Growth of Carbapenem-Resistant E. coli and Targets Cell-Wall Synthesis

  摘要：

  The emergence of multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae, is a major health problem that necessitates the development of new antibiotics. Vancomycin inhibits cell-wall synthesis in Gram-positive bacteria but is generally ineffective against Gram-negative bacteria and is unable to penetrate the outer membrane barrier. In an effort to determine whether vancomycin and other antibiotics effective against Gram-positive bacteria could, through modification, be rendered effective against Gram-negative bacteria, we discovered that the covalent attachment of a single arginine to vancomycin yielded conjugates with order-of-magnitude improvements in activity against Gram-negative bacteria, including pathogenic E. coli. The vancomycin-arginine conjugate (V-R) exhibited efficacy against actively growing bacteria, induced the loss of rod cellular morphology, and resulted in the intracellular accumulation of peptidoglycan precursors, all consistent with cell-wall synthesis disruption as its mechanism of action. Membrane permeabilization studies demonstrated an enhanced outer membrane permeability of V-R as compared with vancomycin. The conjugate exhibited no mammalian cell toxicity or hemolytic activity in MTT and hemolysis assays. Our study introduces a new vancomycin derivative effective against Gram-negative bacteria and underscores the broader potential of generating new antibiotics through combined mode-of-action and synthesis-informed design studies.

  DOI：

  10.1021/acschembio.9b00565

文献信息

• Conformational Preference in Bis(porphyrin) Tweezer Complexes: A Versatile Chirality Sensor for α-Chiral Carboxylic Acids
  作者：Marina Tanasova、Babak Borhan

  DOI：10.1002/ejoc.201200147

  日期：2012.6

  determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated

  金属化卟啉镊子已表现出非凡的能力，可以作为许多不同类别有机分子的绝对立体化学报告者。然而，结合的灵活性可能导致不同激子耦合圆二色性 (ECCD) 活性构象的集合，这可能导致可变的结果。发现接头灵活性是结合构象的关键决定因素。实验结果表明，接头柔韧性和刚性之间的平衡可以产生最佳的卟啉镊子，稳定所有结合手性客体的共同构象。这导致了一种更简单的方法来确定小有机分子的不对称性的绝对立体化学。
• Vancomycin–Arginine Conjugate Inhibits Growth of Carbapenem-Resistant <i>E. coli</i> and Targets Cell-Wall Synthesis
  作者：Alexandra Antonoplis、Xiaoyu Zang、Tristan Wegner、Paul A. Wender、Lynette Cegelski

  DOI：10.1021/acschembio.9b00565

  日期：2019.9.20

  The emergence of multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae, is a major health problem that necessitates the development of new antibiotics. Vancomycin inhibits cell-wall synthesis in Gram-positive bacteria but is generally ineffective against Gram-negative bacteria and is unable to penetrate the outer membrane barrier. In an effort to determine whether vancomycin and other antibiotics effective against Gram-positive bacteria could, through modification, be rendered effective against Gram-negative bacteria, we discovered that the covalent attachment of a single arginine to vancomycin yielded conjugates with order-of-magnitude improvements in activity against Gram-negative bacteria, including pathogenic E. coli. The vancomycin-arginine conjugate (V-R) exhibited efficacy against actively growing bacteria, induced the loss of rod cellular morphology, and resulted in the intracellular accumulation of peptidoglycan precursors, all consistent with cell-wall synthesis disruption as its mechanism of action. Membrane permeabilization studies demonstrated an enhanced outer membrane permeability of V-R as compared with vancomycin. The conjugate exhibited no mammalian cell toxicity or hemolytic activity in MTT and hemolysis assays. Our study introduces a new vancomycin derivative effective against Gram-negative bacteria and underscores the broader potential of generating new antibiotics through combined mode-of-action and synthesis-informed design studies.