4-(benzimidazol-1-yl)-2-aminobutanoic acid | 1430882-18-0

• 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: 4-(benzimidazol-1-yl)-2-aminobutanoic acid
• 英文别名: (2S)-2-amino-4-(benzimidazol-1-yl)butanoic acid
• CAS: 1430882-18-0
• 化学式: C₁₁H₁₃N₃O₂
• 分子量: 219.243
• InChiKey: CQVUDPOAHFIFAF-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(benzimidazol-1-yl)-2-aminobutanoic acid 在 盐酸 作用下， 以 水 为溶剂， 反应 12.0h， 以0.51 g的产率得到4-(benzimidazol-1-yl)-2-aminobutanoic acid hydrochloride
  参考文献：
  名称：

  Benzimidazole analogs ofl-tryptophan are substrates and inhibitors of tryptophan indole lyase fromEscherichia coli

  摘要：

  Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from l‐tryptophan (l‐Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. β‐(Benzimidazol‐1‐yl)‐l‐alanine (BZI‐Ala), 2‐amino‐4‐(benzimidazol‐1‐yl)butyric acid (homo‐BZI‐Ala) and 2‐amino‐5‐(benzimidazol‐1‐yl)pentanoic acid (bishomo‐BZI‐Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI‐Ala is a good substrate of TIL, with Km = 300 μm, kcat = 5.6 s−1 and kcat/Km = 1.9 × 104, similar to l‐Trp. BZI‐Ala is also a good substrate for H463F mutant TIL, which has very low activity with l‐Trp. In contrast, homo‐BZI‐Ala was found to be a potent competitive inhibitor of TIL, with a Ki of 13.4 μm. However, the higher homolog, bishomo‐BZI‐Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, and is thus a much weaker inhibitor. The reaction of TIL with BZI‐Ala was too fast to be observed in the stopped‐flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo‐BZI‐Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem‐diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo‐BZI‐Ala may be due to it being a ‘bi‐product’ analog of the indole‐α‐aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.

  DOI：

  10.1111/febs.12205
• 作为产物：
  描述：

  甲酸 、 2-(benzyloxycarbonylamino)-4-(2'-nitrophenylamino)butanoic acid 在 锌 作用下， 反应 24.0h， 生成 4-(benzimidazol-1-yl)-2-aminobutanoic acid
  参考文献：
  名称：

  Benzimidazole analogs ofl-tryptophan are substrates and inhibitors of tryptophan indole lyase fromEscherichia coli

  摘要：

  Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from l‐tryptophan (l‐Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. β‐(Benzimidazol‐1‐yl)‐l‐alanine (BZI‐Ala), 2‐amino‐4‐(benzimidazol‐1‐yl)butyric acid (homo‐BZI‐Ala) and 2‐amino‐5‐(benzimidazol‐1‐yl)pentanoic acid (bishomo‐BZI‐Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI‐Ala is a good substrate of TIL, with Km = 300 μm, kcat = 5.6 s−1 and kcat/Km = 1.9 × 104, similar to l‐Trp. BZI‐Ala is also a good substrate for H463F mutant TIL, which has very low activity with l‐Trp. In contrast, homo‐BZI‐Ala was found to be a potent competitive inhibitor of TIL, with a Ki of 13.4 μm. However, the higher homolog, bishomo‐BZI‐Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, and is thus a much weaker inhibitor. The reaction of TIL with BZI‐Ala was too fast to be observed in the stopped‐flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo‐BZI‐Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem‐diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo‐BZI‐Ala may be due to it being a ‘bi‐product’ analog of the indole‐α‐aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.

  DOI：

  10.1111/febs.12205

文献信息

• Benzimidazole analogs of<scp>l</scp>-tryptophan are substrates and inhibitors of tryptophan indole lyase from<i>Escherichia coli</i>
  作者：Austin P. Harris、Robert S. Phillips

  DOI：10.1111/febs.12205

  日期：2013.4

  Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from l‐tryptophan (l‐Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. β‐(Benzimidazol‐1‐yl)‐l‐alanine (BZI‐Ala), 2‐amino‐4‐(benzimidazol‐1‐yl)butyric acid (homo‐BZI‐Ala) and 2‐amino‐5‐(benzimidazol‐1‐yl)pentanoic acid (bishomo‐BZI‐Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI‐Ala is a good substrate of TIL, with Km = 300 μm, kcat = 5.6 s−1 and kcat/Km = 1.9 × 104, similar to l‐Trp. BZI‐Ala is also a good substrate for H463F mutant TIL, which has very low activity with l‐Trp. In contrast, homo‐BZI‐Ala was found to be a potent competitive inhibitor of TIL, with a Ki of 13.4 μm. However, the higher homolog, bishomo‐BZI‐Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, and is thus a much weaker inhibitor. The reaction of TIL with BZI‐Ala was too fast to be observed in the stopped‐flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo‐BZI‐Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem‐diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo‐BZI‐Ala may be due to it being a ‘bi‐product’ analog of the indole‐α‐aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.