methyl 2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-6-O-benzyl-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside | 666728-59-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-6-O-benzyl-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside
• 英文别名: (2R)-2-[(2R,3R,4R,5S,6R)-5-[[(2R,4aR,6S,7R,8R,8aS)-7-acetamido-2-phenyl-8-phenylmethoxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-3-acetamido-2-methoxy-6-(phenylmethoxymethyl)oxan-4-yl]oxypropanoic acid
• CAS: 666728-59-2
• 化学式: C₄₁H₅₀N₂O₁₃
• 分子量: 778.854
• InChiKey: BTDFMZUQQOIUKE-SMOWZAJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  56
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-6-O-benzyl-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside 在 溶剂黄146 、 palladium on activated carbon 、 氢气 作用下， 反应 20.0h， 以64%的产率得到(2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-3-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxypropanoic acid
  参考文献：
  名称：

  从基因组到蛋白质组，再到铜绿假单胞菌所有十一种已知的赖氨酸转糖基酶的反应阐明

  摘要：

  酶超家族，即溶菌转糖基酶（LTs），占据了革兰氏阴性细菌两膜之间的空间。LTs催化细菌肽聚糖细胞壁聚合物的非水解裂解。该反应对于细胞壁的生长至关重要，可用于挖掘细胞壁以插入蛋白质，并用于监测细胞壁，从而引发对具有细胞壁作用的抗生素的抗药性反应。凶恶的革兰氏阴性病菌铜绿假单胞菌编码11个LT。除少数例外，它们的底物和功能未知。每个铜绿假单胞菌LT表达为可溶性蛋白，并用一组底物（天然底物的简单和复杂模拟物）进行评估。31种不同的产品在底物识别，催化活性以及相对的内溶或内溶能力方面对这些LT进行了区分。这些特性是将LT作为催化剂和抗生素靶标的基础。

  DOI：

  10.1002/anie.201611279
• 作为产物：
  描述：

  methyl 2-acetamido-3-O-acetyl-6-O-benzyl-2-deoxy-β-D-glucopyranoside 在 吡啶 、 sodium hydroxide 、 三氟甲磺酸三甲基硅酯 、 4 A molecular sieve 、 4 Angstroem molecular seives 、 sodium methylate 、 sodium hydride 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 methyl 2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-6-O-benzyl-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside
  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

• Activation for Catalysis of Penicillin-Binding Protein 2a from Methicillin-Resistant <i>Staphylococcus </i><i>a</i><i>ureus</i> by Bacterial Cell Wall
  作者：Cosimo Fuda、Dusan Hesek、Mijoon Lee、Ken-ichiro Morio、Thomas Nowak、Shahriar Mobashery

  DOI：10.1021/ja0434376

  日期：2005.2.1

  Methicillin-resistant Staphylococcus aureus (MRSA) has acquired a unique penicillin-binding protein (PBP), PBP 2a, which has rendered the organism resistant to the action of all available beta-lactam antibiotics. The X-ray structure of PBP 2a shows the active site in a closed conformation, consistent with resistance to inhibition by beta-lactam antibiotics. However, it is known that PBP 2a avidly cross-links the S. aureus cell wall, which is its physiological function. It is shown herein that synthetic fragments of the bacterial cell wall bind in a saturable manner to PBP 2a and cause a conformational change in the protein that makes the active site more accessible to binding to a beta-lactam antibiotic. These observations and measurements point to a novel strategy by nature to keep the active site of PBP 2a sheltered from the inhibitory activity of the antibiotics, yet it becomes available to the polymeric cell wall by a requisite conformational change for the critical cell wall cross-linking reaction.