((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methylhydrogen 2-oxo-6-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)hexylphosphonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: ((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methylhydrogen 2-oxo-6-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)hexylphosphonate
• 英文别名: biotin β-ketophosphonate-5'-AMP；[6-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-2-oxohexyl]-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]phosphinic acid;azane
• 化学式: C₂₁H₃₀N₇O₈PS*H₃N
• 分子量: 588.582
• InChiKey: XKOWCMHUPUQQEP-KIRGPYDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.31
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  250
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  D-生物素甲酯 在 吡啶 、 4-二甲氨基吡啶 、 正丁基锂 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三氟乙酸 、 lithium bromide 作用下， 以 四氢呋喃 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 21.08h， 生成 ((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methylhydrogen 2-oxo-6-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)hexylphosphonate
  参考文献：
  名称：

  β-Keto and β-hydroxyphosphonate analogs of biotin-5′-AMP are inhibitors of holocarboxylase synthetase

  摘要：

  Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (beta-ketoP) and hydroxyphosphonate (beta-hydroxyP) analogs of biotin-5'- AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 mu M and 203.7 mu M. By comparison, an IC50 value of 7 mu M was observed with the previously reported biotinol-5'-AMP. The K-i values, 3.4 mu M and 17.3 mu M, respectively, are consistent with the IC50 results, and close to the K-i obtained for biotinol-5'-AMP (7 mu M). The beta-ketoP and b-hydroxyP molecules are competitive inhibitors of HLCS while biotinol-5'-AMP inhibited HLCS by a mixed mechanism. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.11.010

文献信息

• β-Keto and β-hydroxyphosphonate analogs of biotin-5′-AMP are inhibitors of holocarboxylase synthetase
  作者：Wantanee Sittiwong、Elizabeth L. Cordonier、Janos Zempleni、Patrick H. Dussault

  DOI：10.1016/j.bmcl.2014.11.010

  日期：2014.12

  Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (beta-ketoP) and hydroxyphosphonate (beta-hydroxyP) analogs of biotin-5'- AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 mu M and 203.7 mu M. By comparison, an IC50 value of 7 mu M was observed with the previously reported biotinol-5'-AMP. The K-i values, 3.4 mu M and 17.3 mu M, respectively, are consistent with the IC50 results, and close to the K-i obtained for biotinol-5'-AMP (7 mu M). The beta-ketoP and b-hydroxyP molecules are competitive inhibitors of HLCS while biotinol-5'-AMP inhibited HLCS by a mixed mechanism. (C) 2014 Elsevier Ltd. All rights reserved.