(S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carboxylic acid methylamide | 745009-88-5

• 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: (S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carboxylic acid methylamide
• 英文别名: Ala-Pro-NH-CH3；(2S)-1-[(2S)-2-aminopropanoyl]-N-methylpyrrolidine-2-carboxamide
• CAS: 745009-88-5
• 化学式: C₉H₁₇N₃O₂
• 分子量: 199.253
• InChiKey: NIQSFBXODLISCO-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carboxylic acid methylamide 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  设计，合成和体外生物学靶向大肠杆菌I型信号肽酶（LepB）的寡肽

  摘要：

  I型信号肽酶是开发新抗菌剂的潜在目标。在这里，我们报告通过优化N-和C-末端的修饰来优化先前报道的热门化合物癸酰-PTANA-CHO，从而发现了I型大肠杆菌信号肽酶（LepB）的有效抑制剂。使用IC 50可获得抑制力的良好改善在低纳摩尔范围内。最好的抑制剂还显示出良好的抗菌活性，对于几种细菌，MICs在低μg/ mL范围内。抗性突变体的选择为LepB作为这些化合物的靶标提供了有力的支持。这些化合物的细胞毒性和溶血特性不是最佳的，但是微小的结构变化对这些特性产生较大影响的发现表明，在未来的研究中存在优化的潜力。

  DOI：

  10.1016/j.bmc.2016.12.003
• 作为产物：
  描述：

  L-proline methylamide 在 哌啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.42h， 生成 (S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carboxylic acid methylamide
  参考文献：
  名称：

  设计，合成和体外生物学靶向大肠杆菌I型信号肽酶（LepB）的寡肽

  摘要：

  I型信号肽酶是开发新抗菌剂的潜在目标。在这里，我们报告通过优化N-和C-末端的修饰来优化先前报道的热门化合物癸酰-PTANA-CHO，从而发现了I型大肠杆菌信号肽酶（LepB）的有效抑制剂。使用IC 50可获得抑制力的良好改善在低纳摩尔范围内。最好的抑制剂还显示出良好的抗菌活性，对于几种细菌，MICs在低μg/ mL范围内。抗性突变体的选择为LepB作为这些化合物的靶标提供了有力的支持。这些化合物的细胞毒性和溶血特性不是最佳的，但是微小的结构变化对这些特性产生较大影响的发现表明，在未来的研究中存在优化的潜力。

  DOI：

  10.1016/j.bmc.2016.12.003

文献信息

• MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
  申请人：RQx Pharmaceuticals, Inc.

  公开号：US20140142029A1

  公开（公告）日：2014-05-22

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。在各种实施例中，这些化合物通过抑制细菌类型1信号肽酶（SpsB）来发挥作用，该酶是细菌中的一种必需蛋白质。同时还提供了使用所述化合物的药物组合物和治疗方法。
• Method for the use and synthesis of peptides
  申请人：Chiron Corporation

  公开号：US05783674A1

  公开（公告）日：1998-07-21

  A method for the separation of at least one specific binding entity from a mixture of binding entities by the steps of contacting a mixture of binding entities with immobilized peptides in which the peptides specifically bind to the specific binding entities and the peptides contain an amino acid which facilitates removal of the binding entities from the peptides, and separating the immobilized peptide/specific binding entity complexes from the mixture of binding entities. A change in incubation conditions facilitates removal of the binding entities from the immobilized peptides.

  一种用于从结合实体混合物中分离至少一种特定结合实体的方法，包括以下步骤：将结合实体混合物与固定化肽接触，其中肽特异性结合于特定结合实体，且肽包含一种氨基酸，可促进从肽中去除结合实体，并将固定化的肽/特定结合实体复合物从结合实体混合物中分离。孵育条件的改变有助于从固定化肽中去除结合实体。
• Pseudo-Prolines as a Molecular Hinge:  Reversible Induction of <i>cis</i> Amide Bonds into Peptide Backbones
  作者：Pascal Dumy、Michael Keller、Declan E. Ryan、Barbara Rohwedder、Torsten Wöhr、Manfred Mutter

  DOI：10.1021/ja962780a

  日期：1997.2.1

  Serine, threonine-derived (4S)-oxazolidine-4-carboxylic acid, and cysteine-derived (4R)-thiazolidinecarboxylic acid, denoted pseudo-proline (Xaa[Psi(R1,R2)pro]), serve as structure disrupting, solubilizing building blocks in peptide synthesis. Variation of the 2-C substituents within the heterocyclic system results in different physicochemical and conformational properties. NMR studies of a series of pseudo-proline (Psi Pro)-containing peptides reveal a pronounced effect of the 2-C substituents upon the cis to trans ratio of the adjacent amide bond in solution. 2-C unsubstituted systems show a preference similar to that of the proline residue for the trans form, whereas 2,2-dimethylated derivatives adopt the cis amide conformation in high content. For 2-monosubstituted Psi Pro, the cis-trans distribution depends on the 2-C chirality. For the 2-(S)-diastereoisomer, both forms are similarly populated in solution, whereas the 2-(R)-epimer adopts preferentially the trans form. The results are supported by conformational energy calculations and suggest that, by tailoring the degree of substitution, pseudo-prolines may serve as a temporary proline mimetic or as a hinge in peptide backbones.
• Further Evidence for 2-Alkyl-2-carboxyazetidines as γ-Turn Inducers
  作者：José Luis Baeza、Guillermo Gerona-Navarro、Kevin Thompson、M. Jesús Pérez de Vega、Lourdes Infantes、M. Teresa García-López、Rosario González-Muñiz、Mercedes Martín-Martínez

  DOI：10.1021/jo901712x

  日期：2009.11.6

  Reverse turns, it common motif in proteins and peptides, have attracted attention due to their relevance in it Wide variety of biological processes. In in attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines, and incorporated them into the i + 1 position of model tetrapeptides, where they have shown it tendency to induce gamma-turns However, to ascertain the general utility of these restricted amino acids its gamma-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently Substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and Subjected to it thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce gamma-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.
• US9309285B2
  申请人：——

  公开号：US9309285B2

  公开（公告）日：2016-04-12