retinylimine | 23352-58-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: retinylimine
• 英文别名: trans-Retinylidin amin；(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraen-1-imine
• CAS: 23352-58-1
• 化学式: C₂₀H₂₉N
• 分子量: 283.457
• InChiKey: VGVRTZOYKRWJLY-ULABPGQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.8
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  retinylimine 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-amine
  参考文献：
  名称：

  Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

  摘要：

  Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included -helix II and hairpin turns between -strands C-D and E-F as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins.

  DOI：

  10.1074/jbc.m116.714535
• 作为产物：
  描述：

  视黄醛 在 氨 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 retinylimine
  参考文献：
  名称：

  Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

  摘要：

  Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included -helix II and hairpin turns between -strands C-D and E-F as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins.

  DOI：

  10.1074/jbc.m116.714535

文献信息

• [EN] RETINYLAMINE DERIVITIVES FOR TREATMENT OF OCULAR DISORDERS<br/>[FR] DÉRIVÉS DE RÉTINYLAMINE POUR LE TRAITEMENT DE TROUBLES OCULAIRES
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2015184453A1

  公开（公告）日：2015-12-03

  A pharmaceutical composition includes a retinylamine derivative having the following formula (I): where R1 is an amino acid residue, a dipeptide or a tripeptide that is linked to the retinylamine by an amide bond.

  一种制药组合物包括以下式子(I)的视黄醛胺衍生物，其中R1是与视黄醛胺通过酰胺键连接的氨基酸残基、二肽或三肽。
• Retinylamine derivitives for treatment of ocular disorders
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US10471118B2

  公开（公告）日：2019-11-12

  A pharmaceutical composition includes a retinylamine derivative having the following formula (I): where R1 is an amino acid residue, a dipeptide or a tripeptide that is linked to the retinylamine by an amide bond.

  一种药物组合物包括具有下式（I）的视黄醇胺衍生物： 其中 R1 是通过酰胺键与视黄醇胺相连的氨基酸残基、二肽或三肽。
• WO2006/91761
  申请人：——

  公开号：——

  公开（公告）日：——
• RETINYLAMINE DERIVITIVES FOR TREATMENT OF OCULAR DISORDERS
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US20170112892A1

  公开（公告）日：2017-04-27

  A pharmaceutical composition includes a retinylamine derivative having the following formula (I): where R 1 is an amino acid residue, a dipeptide or a tripeptide that is linked to the retinylamine by an amide bond.