(2R)-2-[[(2S)-2-[[(2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-6-amino-1-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid | 666728-46-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-[[(2S)-2-[[(2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-6-amino-1-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid
• CAS: 666728-46-7
• 化学式: C₃₂H₅₅N₇O₁₅
• 分子量: 777.827
• InChiKey: JXJKEMJZBRKQFW-VKTOLQJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  54
• 可旋转键数：
  23
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  343
• 氢给体数：
  11
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (2R)-2-[[(2S)-2-[[(2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-6-amino-1-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid 在 catalase Escherichia coli penicillin-binding protein 5 、 HEPES buffer 、 L-lactate dehydrogenase 作用下， 以 水 为溶剂， 生成 D-丙氨酸 、
  参考文献：
  名称：

  Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria

  摘要：

  The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.

  DOI：

  10.1021/jo035397e
• 作为产物：
  描述：

  甲基 2-乙酰氨基-3,4,6-O-三乙酰基-2-脱氧-beta-D-吡喃葡萄糖苷 在 palladium on activated charcoal 吡啶 、 4 A molecular sieve 、 氢气 、 sodium methylate 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 44.5h， 生成 (2R)-2-[[(2S)-2-[[(2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-6-amino-1-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria

  摘要：

  The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.

  DOI：

  10.1021/jo035397e

文献信息

• Thermodynamics of Interactions of Vancomycin and Synthetic Surrogates of Bacterial Cell Wall
  作者：Mikhail Rekharsky、Dusan Hesek、Mijoon Lee、Samy O. Meroueh、Yoshihisa Inoue、Shahriar Mobashery

  DOI：10.1021/ja061828+

  日期：2006.6.1

  vancomycin, form complexes via a set of five hydrogen bonds with the acyl-l-Lys-d-Ala-d-Ala portion of the peptidyl stems of the bacterial cell wall peptidoglycan. This complexation deprives the organism from the ability to cross-link peptidyl stems of the peptidoglycan, leading to bacterial cell death. Four synthetic fragments as surrogates of the components of the bacterial cell wall have been prepared

  糖肽抗生素，包括万古霉素，通过一组五个氢键与细菌细胞壁肽聚糖肽基茎的酰基-L-Lys-d-Ala-d-Ala部分形成复合物。这种络合剥夺了生物体交联肽聚糖肽基茎的能力，导致细菌细胞死亡。我们的实验室通过多步合成制备了四种合成片段作为细菌细胞壁成分的替代物。这些合成样品用于通过等温滴定量热法 (ITC) 研究与万古霉素络合的热力学性质（DeltaG 度、DeltaH 度和 TDeltaS 度）。与糖肽类似物的络合很大程度上是由焓驱动的（形成五个氢键），并且在具有单个肽基茎的类似物中，络合为1:1。大约 2 kDa 的细胞壁替代物（化合物 4）具有两个肽基茎，络合更加复杂。数据表明两个万古霉素分子之间存在相互作用，由于肽基茎的高度移动的酰基-d-Ala-d-Ala部分的运动受到限制，因此导致复合物内分子运动的限制，从而导致熵损失。这些数据与最近确定的肽聚糖片段 4 的 NMR 溶液结构及其对较大细胞壁的影响相一致。