3'-(L-N,N-diacetyllysinyl)amino-3'-deoxyadenosine | 1338916-87-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3'-(L-N,N-diacetyllysinyl)amino-3'-deoxyadenosine
• 英文别名: (2S)-2,6-diacetamido-N-[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]hexanamide
• CAS: 1338916-87-2
• 化学式: C₂₀H₃₀N₈O₆
• 分子量: 478.508
• InChiKey: CPKVBYSZISANFC-GJIZYBQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  207
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-氨基-d-腺苷酸 在 吡啶 、 氟化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 为溶剂， 生成 3'-(L-N,N-diacetyllysinyl)amino-3'-deoxyadenosine
  参考文献：
  名称：

  NMR-Based Substrate Analog Docking to Escherichia coli Peptidyl-tRNA Hydrolase

  摘要：

  Escherichia coli peptidyl-tRNA hydrolase activity is inhibited by 3'-(L-[N,N-diacetyl-lysinyl)amino-3'-deoxyadenosine, a stable mimic of the minimalist substrate 2'(3')-O-(L-[N,N-diacetyl-lysinyl)adenosine. The complex of this mimic with the enzyme has been analyzed by NMR spectroscopy, enabling experimental mapping of the catalytic center for the first time. Chemical shift variations point out the sensitivity of residues Asn10, Met67, Asn68, Gly111, Asn114, Leu116, Lys117, Gly147, Phe148, and Val149 to complex formation. Docking simulations based on ambiguous interaction restraints involving these residues show bondings of the peptide moiety of 3'-(L-[N,N-diacetyl-lysinyl)amino-3'-deoxyadenosine with Asn10, Asn68, and Asn114. A stacking interaction of Phe66 with the purine is also indicated. Drawn is a model of enzyme-bound peptidyl-tRNA substrate, in which: (i) the Asn114 delta(2) NH(2) group holds the water molecule that participates in the hydrolysis of the substrate, while Tyr15 binds the phosphate in the 5'-position of the 3'-terminal tRNA adenosine; (ii) the delta(2) NH(2) group of Asn68 holds the mainchain carbonyl of the C-terminal residue of the peptide esterified to tRNA; and (iii) the delta(2) NH(2) group of Asn10 holds the main-chain carbonyl of the penultimate C-residue. Functional value is given to this model by (i) showing that the enzyme becomes confusable with an aminoacyl-tRNA hydrolase upon mutagenesis of Asn10 and (ii) reinterpreting already obtained site-directed mutagenesis data. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.jmb.2011.06.025

文献信息

• NMR-Based Substrate Analog Docking to Escherichia coli Peptidyl-tRNA Hydrolase
  作者：Laurent Giorgi、Pierre Plateau、Gavin O'Mahony、Caroline Aubard、Michel Fromant、Aurélien Thureau、Morten Grøtli、Sylvain Blanquet、François Bontems

  DOI：10.1016/j.jmb.2011.06.025

  日期：2011.9

  Escherichia coli peptidyl-tRNA hydrolase activity is inhibited by 3'-(L-[N,N-diacetyl-lysinyl)amino-3'-deoxyadenosine, a stable mimic of the minimalist substrate 2'(3')-O-(L-[N,N-diacetyl-lysinyl)adenosine. The complex of this mimic with the enzyme has been analyzed by NMR spectroscopy, enabling experimental mapping of the catalytic center for the first time. Chemical shift variations point out the sensitivity of residues Asn10, Met67, Asn68, Gly111, Asn114, Leu116, Lys117, Gly147, Phe148, and Val149 to complex formation. Docking simulations based on ambiguous interaction restraints involving these residues show bondings of the peptide moiety of 3'-(L-[N,N-diacetyl-lysinyl)amino-3'-deoxyadenosine with Asn10, Asn68, and Asn114. A stacking interaction of Phe66 with the purine is also indicated. Drawn is a model of enzyme-bound peptidyl-tRNA substrate, in which: (i) the Asn114 delta(2) NH(2) group holds the water molecule that participates in the hydrolysis of the substrate, while Tyr15 binds the phosphate in the 5'-position of the 3'-terminal tRNA adenosine; (ii) the delta(2) NH(2) group of Asn68 holds the mainchain carbonyl of the C-terminal residue of the peptide esterified to tRNA; and (iii) the delta(2) NH(2) group of Asn10 holds the main-chain carbonyl of the penultimate C-residue. Functional value is given to this model by (i) showing that the enzyme becomes confusable with an aminoacyl-tRNA hydrolase upon mutagenesis of Asn10 and (ii) reinterpreting already obtained site-directed mutagenesis data. (C) 2011 Published by Elsevier Ltd.