(2S,3R,4R)-2,3,4-trihydroxy-6-phosphonohexanoic acid | 603993-43-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (2S,3R,4R)-2,3,4-trihydroxy-6-phosphonohexanoic acid
• CAS: 603993-43-7
• 化学式: C₆H₁₃O₈P
• 分子量: 244.138
• InChiKey: AJDVEYQJAPQAOC-WDCZJNDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  156
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R)-2,3,4-trihydroxy-6-phosphonohexanoic acid 在 Dowex-50WX₈ (Na+) 作用下， 以 水 为溶剂， 以215 mg的产率得到5-deoxy-5-phosphonomethyl-D-arabinonate trisodium salt
  参考文献：
  名称：

  Synthesis and evaluation of non-hydrolyzable d-mannose 6-phosphate surrogates reveal 6-deoxy-6-dicarboxymethyl-d-mannose as a new strong inhibitor of phosphomannose isomerases

  摘要：

  Non-hydrolyzable D-mannose 6-phosphate analogues in which the phosphate group was replaced by a phosphonomethyl, a dicarboxymethyl, or a carboxymethyl group were synthesized and kinetically evaluated as substrate analogues acting as potential inhibitors of type I phosphomannose isomerases (PMIs) from Saccharomyces cerevisiae and Escherichia coli. While 6-deoxy-6-phosphonomethyl-D-mannose and 6-deoxy-6-carboxymethyl-D-mannose did not inhibit the enzymes significantly, 6-deoxy-6-dicarboxymethyl-D-mannose appeared as a new strong competitive inhibitor of both S. cerevisiae and E. coli PMIs with K-m/K-i ratios of 28 and 8, respectively. We thus report the first malonate-based inhibitor of an aldose-ketose isomerase to date. Phosphonomethyl mimics of the 1,2-cis-enediolate high-energy intermediate postulated for the isomerization reaction catalyzed by PMIs were also synthesized but behave as poor inhibitors of PMIs. A polarizable molecular mechanics (SIBFA) study was performed on the complexes of D-mannose 6-phosphate and two of its analogues with PMI from Candida albicans, an enzyme involved in yeast infection homologous to S. cerevisiae and E. coli PMIs. It shows that effective binding to the catalytic site occurs with retention of the Zn(II)-bound water molecule. Thus the binding of the hydroxyl group on C1 of the ligand to Zn(II) should be water-mediated. The kinetic study reported here also suggests the dianionic character of the phosphate surrogate as a likely essential parameter for strong binding of the inhibitor to the enzyme active site. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.005
• 作为产物：
  描述：

  6-deoxy-6-phosphonomethyl-D-mannopyranose dipotassium salt 在 氧气 、 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 168.0h， 生成 (2S,3R,4R)-2,3,4-trihydroxy-6-phosphonohexanoic acid
  参考文献：
  名称：

  Synthesis and evaluation of non-hydrolyzable d-mannose 6-phosphate surrogates reveal 6-deoxy-6-dicarboxymethyl-d-mannose as a new strong inhibitor of phosphomannose isomerases

  摘要：

  Non-hydrolyzable D-mannose 6-phosphate analogues in which the phosphate group was replaced by a phosphonomethyl, a dicarboxymethyl, or a carboxymethyl group were synthesized and kinetically evaluated as substrate analogues acting as potential inhibitors of type I phosphomannose isomerases (PMIs) from Saccharomyces cerevisiae and Escherichia coli. While 6-deoxy-6-phosphonomethyl-D-mannose and 6-deoxy-6-carboxymethyl-D-mannose did not inhibit the enzymes significantly, 6-deoxy-6-dicarboxymethyl-D-mannose appeared as a new strong competitive inhibitor of both S. cerevisiae and E. coli PMIs with K-m/K-i ratios of 28 and 8, respectively. We thus report the first malonate-based inhibitor of an aldose-ketose isomerase to date. Phosphonomethyl mimics of the 1,2-cis-enediolate high-energy intermediate postulated for the isomerization reaction catalyzed by PMIs were also synthesized but behave as poor inhibitors of PMIs. A polarizable molecular mechanics (SIBFA) study was performed on the complexes of D-mannose 6-phosphate and two of its analogues with PMI from Candida albicans, an enzyme involved in yeast infection homologous to S. cerevisiae and E. coli PMIs. It shows that effective binding to the catalytic site occurs with retention of the Zn(II)-bound water molecule. Thus the binding of the hydroxyl group on C1 of the ligand to Zn(II) should be water-mediated. The kinetic study reported here also suggests the dianionic character of the phosphate surrogate as a likely essential parameter for strong binding of the inhibitor to the enzyme active site. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.005

文献信息

• COMPOSITIONS AND METHODS TO BOOST ENDOGENOUS ROS PRODUCTION FROM BACTERIA
  申请人：Trustees of Boston University

  公开号：US20150071904A1

  公开（公告）日：2015-03-12

  Provided herein are compositions and methods comprising ROS target modulators that increase ROS flux and endogenus ROS production, thereby potentiating oxidative attack by antibiotics and biocides.
• [EN] COMPOSITIONS AND METHODS TO BOOST ENDOGENOUS ROS PRODUCTION FROM BACTERIA<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR AMPLIFIER LA PRODUCTION ENDOGÈNE D'ESPÈCES RÉACTIVES DE L'OXYGÈNE (ROS) À PARTIR DE BACTÉRIES
  申请人：UNIV BOSTON

  公开号：WO2013103780A1

  公开（公告）日：2013-07-11

  Provided herein are compositions and methods comprising ROS target modulators that increase ROS flux and endogenous ROS production, thereby potentiating oxidative attack by antibiotics and biocides.