di-tert-butyl 7-(2-aminoethyl)-1-oxa-4,7,10-triazacyclododecane-4,10-dicarboxylate | 1233487-03-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: di-tert-butyl 7-(2-aminoethyl)-1-oxa-4,7,10-triazacyclododecane-4,10-dicarboxylate
• CAS: 1233487-03-0
• 化学式: C₂₀H₄₀N₄O₅
• 分子量: 416.561
• InChiKey: VCLTZFMUMSMBDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  29.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  97.57
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (4-benzooxazol-2-yl-benzyl)-(4,6-dichloro-[1,3,5]triazin-2-yl)-amine 、 di-tert-butyl 7-(2-aminoethyl)-1-oxa-4,7,10-triazacyclododecane-4,10-dicarboxylate 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  New chelating ligands for Co(III)-based peptide-cleaving catalysts selective for pathogenic proteins of amyloidoses

  摘要：

  The Co(III) complex of 1,4,7,10-tetraazacyclododecane has been employed as the catalytic center of target-selective peptide-cleaving catalysts in previous studies. As new chelating ligands for the Co(III) ion in the peptide-cleaving catalysts, 1-oxo-4,7,10-triazacyclodedecane, 1-aryl-1,4,7,10-tetraazacyclodecane, and 7-aryl-1-oxo-4,7,10-triazacyclodecane were examined in the present study. A chemical library comprising 612 derivatives of the Co(III) complex of the new chelating ligands was constructed. The catalyst candidates were tested for their activity to cleave the soluble oligomers of amyloidogenic peptides amyloid beta-42 and human islet amyloid polypeptide (h-IAPP), which are believed to be the pathogenic species for Alzheimer's disease and type 2 diabetes mellitus, respectively. One derivative of the Co(III) complex of 1-aryl-1,4,7,10-tetraazacyclodecane was found to cleave the oligomers of h-IAPP. Cleavage products were identified and cleavage yields were measured at various catalyst concentrations for the action of the new catalyst. The present results reveal that effective catalytic drugs for amyloidoses may be obtained by using Co(III) complexes of various chelating ligands.

  DOI：

  10.1007/s00775-010-0750-y

文献信息

• Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, and high thermal and chemical stabilities
  作者：Min Gyum Kim、Sang Ho Yoo、Woo Suk Chei、Tae Yeon Lee、Hye Mi Kim、Junghun Suh

  DOI：10.1007/s00775-010-0662-x

  日期：2010.9

  artificial protease and the protein substrate was supported by an experiment using sodium cyanoborohydride. Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, high thermal and chemical stabilities, and small molecular weights were thus synthesized by positioning the aldehyde group in proximity to Cu(II) oxacyclen.

  为了设计可切割各种具有高反应性的蛋白质的肽主链的可溶性人工蛋白酶，合成了包含 1-oxa-4,7,10-三氮杂环十二烷 (oxacyclen) 和醛基的 Cu(II) 复合物的人工活性位点. 鉴于醛基能够与暴露在蛋白质表面的铵基可逆地形成亚胺键，因此采用醛基作为结合位点，并利用 Cu(II) oxacyclen 作为肽水解的催化基团。本研究中合成的人工金属蛋白酶裂解了所有检测的蛋白质底物（白蛋白、γ-球蛋白、肌红蛋白和溶菌酶）。此外，以 kcat/Km 计算，最佳可溶性人工蛋白酶的活性提高了 190 倍。当温度升至80摄氏度时，人工蛋白酶的活性显着增强。人工蛋白酶的活性不受表面活性剂，包括十二烷基硫酸钠的很大影响。在人工蛋白酶和蛋白质底物之间形成的亚胺复合物的中介作用得到了使用氰基硼氢化钠的实验的支持。因此，通过将醛基定位在 Cu(II) oxacyclen 附近，合成了具有广泛底物选择性