benzyl N-[(2S)-4-methyl-1-[7-[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-1-oxopentan-2-yl]carbamate | 1357257-64-7

• 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: benzyl N-[(2S)-4-methyl-1-[7-[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-1-oxopentan-2-yl]carbamate
• CAS: 1357257-64-7
• 化学式: C₃₅H₄₈N₄O₆
• 分子量: 620.789
• InChiKey: OGRQYTPWNXGMHE-NPYONTDKSA-N

物化性质

• 熔点：
  156-157 °C
• 沸点：
  800.6±65.0 °C(predicted)
• 密度：
  1.169±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-L-亮氨酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 benzyl N-[(2S)-4-methyl-1-[7-[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Bispidine as a secondary structure nucleator in peptides

  摘要：

  Here we describe bispidine as a scaffold for inducing open turn-like and beta sheet conformations on the attached peptides depending on the mode of attachment of peptides to the scaffold. Various bispidine-peptide conjugates were designed and synthesized to demonstrate the versatility of the scaffold. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.11.112

文献信息

• Modulation of prion polymerization and toxicity by rationally designed peptidomimetics
  作者：Ankit Srivastava、Sakshi Sharma、Sandhya Sadanandan、Sakshi Gupta、Jasdeep Singh、Sarika Gupta、V. Haridas、Bishwajit Kundu

  DOI：10.1042/bcj20160737

  日期：2017.1.1

  Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2–β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity.

  细胞朊病毒蛋白的错误折叠和聚集与一系列神经系统疾病有关，这些疾病通常被称为传染性海绵状脑病。由于有关朊病毒致病自组装机制的信息有限，设计朊病毒抑制剂一直是一项艰巨的任务。在这里，我们探讨了基于双脒的拟肽化合物（BPMs）组合库的抗朊病毒特性，该化合物将氨基酸与疏水侧链和芳香侧链结合在一起。在保持双脒单元不变的情况下，合成了一系列结构多样的 BPM，并对其朊病毒调节特性进行了测试。服用 Leu- 和 Trp-BPMs 可分别延迟和完全抑制人朊病毒蛋白（HuPrP）的淀粉样转化。我们发现，每种BPM都能诱导HuPrP形成独特的低聚物纳米结构，其生物物理特性、细胞毒性和对构象特异性抗体的反应各不相同。研究发现，Leu-BPM 可稳定低聚物，而 Trp-BPM 则可实现瞬时低聚，从而形成无毒的非纤维状聚集体。然而，另一种芳香族残基 Phe 会加速 HuPrP 的聚集过程。通过 MD（分子动力学）模拟获得的分子见解表明，每一种 BPM 都以不同的方式与 HuPrP α2-β2 环上的保守 Tyr 169 残基结合，并影响 α2 和 α3 螺旋的稳定性。我们的研究结果表明，这一类新分子具有连接疏水/芳香残基的化学支架，可有效调节朊病毒的聚集和毒性。
• Bispidine as a secondary structure nucleator in peptides
  作者：V. Haridas、Sandhya Sadanandan、Yogesh K. Sharma、Srinivas Chinthalapalli、Ashutosh Shandilya

  DOI：10.1016/j.tetlet.2011.11.112

  日期：2012.2

  Here we describe bispidine as a scaffold for inducing open turn-like and beta sheet conformations on the attached peptides depending on the mode of attachment of peptides to the scaffold. Various bispidine-peptide conjugates were designed and synthesized to demonstrate the versatility of the scaffold. (C) 2011 Elsevier Ltd. All rights reserved.