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.
• Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria
  作者：Dusan Hesek、Maxim Suvorov、Ken-ichiro Morio、Mijoon Lee、Stephen Brown、Sergei B. Vakulenko、Shahriar Mobashery

  DOI：10.1021/jo035397e

  日期：2004.2.1

  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.
• From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from <i>Pseudomonas aeruginosa</i>
  作者：Mijoon Lee、Dusan Hesek、David A. Dik、Jennifer Fishovitz、Elena Lastochkin、Bill Boggess、Jed F. Fisher、Shahriar Mobashery

  DOI：10.1002/anie.201611279

  日期：2017.3.1

  An enzyme superfamily, the lytic transglycosylases (LTs), occupies the space between the two membranes of Gram‐negative bacteria. LTs catalyze the non‐hydrolytic cleavage of the bacterial peptidoglycan cell‐wall polymer. This reaction is central to the growth of the cell wall, for excavating the cell wall for protein insertion, and for monitoring the cell wall so as to initiate resistance responses

  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。