N-acetyl-β-D-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-D-muramyl peptide | 109460-54-0

• 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: N-acetyl-β-D-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-D-muramyl peptide
• 英文别名: N-acetyl-β-D-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala；N-acetyl-β-D-glucosamine-(1->4)-1,6-anhydro-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala；N-acetyl-β-D-glucosamine-(1->4)-1,6-anhydro-β-D-N-acetylmuramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala；GluNAc-AnhMurNAc-L-Ala-γ-D-Glu-m-DAP-D-Ala-D-Ala；(2R,6S)-6-[[(4R)-4-[[(2S)-2-[[(2R)-2-[[(1R,2S,3R,4R,5R)-4-acetamido-2-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]oxy]propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-2-amino-7-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-7-oxoheptanoic acid
• CAS: 109460-54-0
• 化学式: C₄₀H₆₄N₈O₂₁
• 分子量: 992.989
• InChiKey: XHMAKYORQAVSPY-WSLAIONWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.9
• 重原子数：
  69
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  449
• 氢给体数：
  14
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  N-acetyl-β-D-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-D-muramyl peptide 在 bacterial AmpD protein 作用下， 生成 (2R,6S)-2-amino-6-[[(4R)-4-[[(2S)-2-aminopropanoyl]amino]-4-carboxybutanoyl]amino]-7-[[(2R)-1-[[(1R)-1-carboxyethyl]amino]-1-oxopropan-2-yl]amino]-7-oxoheptanoic acid 、 1,6-anhydro-N-acetylmuramic acid
  参考文献：
  名称：

  Bacterial AmpD at the Crossroads of Peptidoglycan Recycling and Manifestation of Antibiotic Resistance

  摘要：

  The bacterial, enzyme AmpD is an early catalyst in commitment of cell wall metabolites to the recycling events within the cytoplasm. The key internalized metabolite of Cell watt recycling, beta-D-N-acetytgtucosamine-(1 -> 4)-1,6-anhydro-beta-N-acetytmuramyl-L-Ala-gamma-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is a poor substrate for AmpD. Two additional metabolites, 1,6-anhydro-N-acetyimuramyl-peptidyl derivatives 2a and 2c, served as substrates for AmpD with a k(cat)/K-m of >10(4) M-1 s(-1). The enzyme hydrolytically processes the lactyl amide bond of the 1,6-anhydro-N-acetylmuramyl moiety. The syntheses of these substrates and other ligands are reported herein, which made the characterization of the enzymic reaction possible. Furthermore, it is documented that the enzyme is specific for both the atypical peptide stem of the cell wall fragments and the presence of the sterically encumbered 1,6-anhydro-N-acetylmuramyl moiety; hence it is a peptidase with a unique function in bacterial. physiology. The implications of the function of this catalyst for the entry into the cell wall recycling events and the reversal of induction of the production of beta-lactamase, an antibiotic resistance determinant, are discussed.

  DOI：

  10.1021/ja9025566
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 溶剂黄146 、 甲醇 为溶剂， 反应 5.0h， 以66%的产率得到N-acetyl-β-D-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-D-muramyl peptide
  参考文献：
  名称：

  Hesek, Dusan; Lee, Mijoon; Zhang, Weilie, Journal of the American Chemical Society, 2009, vol. 131, p. 5187 - 5193

  摘要：

  DOI：

文献信息

• Reactions of the Three AmpD Enzymes of <i>Pseudomonas aeruginosa</i>
  作者：Weilie Zhang、Mijoon Lee、Dusan Hesek、Elena Lastochkin、Bill Boggess、Shahriar Mobashery

  DOI：10.1021/ja400970n

  日期：2013.4.3

  A group of Gram-negative bacteria, including the problematic pathogen Pseudomonas aeruginosa, has linked the steps in cell-wall recycling with the ability to manifest resistance to beta-lactam antibiotics. A key step at the crossroads of the two events is performed by the protease AmpD, which hydrolyzes the peptide in the metabolite that influences these events. In contrast to other organisms that harbor this elaborate system, the genomic sequences of P. aeruginosa reveal it to have three paralogous genes for this protease, designated as ampD, ampDh2, and ampDh3. The recombinant gene products were purified to homogeneity, and their functions were assessed by the use of synthetic samples of three bacterial metabolites in cell-wall recycling and of three surrogates of cell-wall peptidoglycan. The results unequivocally identify AmpD as the bona fide recycling enzyme and AmpDh2 and AmpDh3 as enzymes involved in turnover of the bacterial cell wall itself. These findings define for the first time the events mediated by these three enzymes that lead to turnover of a key cell-wall recycling metabolite as well as the cell wall itself in its maturation.
• Hesek, Dusan; Lee, Mijoon; Zhang, Weilie, Journal of the American Chemical Society, 2009, vol. 131, p. 5187 - 5193
  作者：Hesek, Dusan、Lee, Mijoon、Zhang, Weilie、Noll, Bruce C.、Mobashery, Shahriar

  DOI：——

  日期：——
• Bacterial AmpD at the Crossroads of Peptidoglycan Recycling and Manifestation of Antibiotic Resistance
  作者：Mijoon Lee、Weilie Zhang、Dusan Hesek、Bruce C. Noll、Bill Boggess、Shahriar Mobashery

  DOI：10.1021/ja9025566

  日期：2009.7.1

  The bacterial, enzyme AmpD is an early catalyst in commitment of cell wall metabolites to the recycling events within the cytoplasm. The key internalized metabolite of Cell watt recycling, beta-D-N-acetytgtucosamine-(1 -> 4)-1,6-anhydro-beta-N-acetytmuramyl-L-Ala-gamma-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is a poor substrate for AmpD. Two additional metabolites, 1,6-anhydro-N-acetyimuramyl-peptidyl derivatives 2a and 2c, served as substrates for AmpD with a k(cat)/K-m of >10(4) M-1 s(-1). The enzyme hydrolytically processes the lactyl amide bond of the 1,6-anhydro-N-acetylmuramyl moiety. The syntheses of these substrates and other ligands are reported herein, which made the characterization of the enzymic reaction possible. Furthermore, it is documented that the enzyme is specific for both the atypical peptide stem of the cell wall fragments and the presence of the sterically encumbered 1,6-anhydro-N-acetylmuramyl moiety; hence it is a peptidase with a unique function in bacterial. physiology. The implications of the function of this catalyst for the entry into the cell wall recycling events and the reversal of induction of the production of beta-lactamase, an antibiotic resistance determinant, are discussed.