adenosine-2'-(1-aminoethyl)phosphonate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: adenosine-2'-(1-aminoethyl)phosphonate
• 英文别名: 2'-(1-aminoethyl phosphonyl)adenosine；O^2'-[(1-amino-ethyl)-hydroxy-phosphinoyl]-adenosine；(1-amino-ethyl)-phosphonic acid adenosin-2'-yl ester；2'-O-(1-Amino-ethan-1-phosphonyl)-adenosin；[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy-(1-azaniumylethyl)phosphinate
• 化学式: C₁₂H₁₉N₆O₆P
• 分子量: 374.293
• InChiKey: NZGIRQPAAQVTDU-NRJACJQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  192
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2'-(1-(benzyloxycarbonylamino)ethyl phosphonyl)adenosine 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 72.0h， 以3.0 mg的产率得到adenosine-2'-(1-aminoethyl)phosphonate
  参考文献：
  名称：

  Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors

  摘要：

  Ligase MurM catalyses the addition of Ala from alanyl-tRNA(Ala), or Ser from seryl-tRNA(Ser), to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA(Ala) showed no inhibition of MurM, but adenosine 3'-phosphonate analogues showed inhibition of MurM, the most active being a 2'-deoxyadenosine analogue (IC50 100 mu M). Structure/function studies upon this analogue established that modi. cation of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modi. cation of the adenosine 5'-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.028

文献信息

• Adenosine phosphonate inhibitors of lipid II: Alanyl tRNA ligase MurM from Streptococcus pneumoniae
  作者：Elena Cressina、Adrian J. Lloyd、Gianfranco De Pascale、David I. Roper、Christopher G. Dowson、Timothy D.H. Bugg

  DOI：10.1016/j.bmcl.2007.05.071

  日期：2007.8

  Adenosine and 2 '-deoxyadenosine phosphonate transition state analogues act as the first inhibitors for the MurMN/FemABX family of tRNA-dependent ligases implicated in high-level penicillin resistance in Gram-positive bacteria. (c) 2007 Elsevier Ltd. All rights reserved.
• Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors
  作者：Elena Cressina、Adrian J. Lloyd、Gianfranco De Pascale、B. James Mok、Stephen Caddick、David I. Roper、Christopher G. Dowson、Timothy D.H. Bugg

  DOI：10.1016/j.bmc.2009.03.028

  日期：2009.5

  Ligase MurM catalyses the addition of Ala from alanyl-tRNA(Ala), or Ser from seryl-tRNA(Ser), to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA(Ala) showed no inhibition of MurM, but adenosine 3'-phosphonate analogues showed inhibition of MurM, the most active being a 2'-deoxyadenosine analogue (IC50 100 mu M). Structure/function studies upon this analogue established that modi. cation of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modi. cation of the adenosine 5'-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria. (C) 2009 Elsevier Ltd. All rights reserved.