4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)-sulfanylpropyl)}benzoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)-sulfanylpropyl)}benzoic acid
• 英文别名: 4-[(2S,3S)-2-amino-4-[[(2S)-1-[[(2S)-1-(benzylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-4-oxo-3-sulfanylbutyl]benzoic acid
• 化学式: C₄₂H₄₂N₄O₅S
• 分子量: 714.885
• InChiKey: AQGBYLGQCFWKTC-ZQWQDMLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  152
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  L-phenylalanine benzylamide 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)-sulfanylpropyl)}benzoic acid
  参考文献：
  名称：

  Development of Potent Inhibitors of Botulinum Neurotoxin Type B

  摘要：

  Botulinum neurotoxins are the most potent toxins known to date. They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis. There is a great interest in designing antagonists of the action of these toxins. One way is to inhibit their catalytic activity. In this study, we report the design of such inhibitors directed toward BoNT/B. A study of the S-1 subsite specificity, using several beta-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety. The specificity of the S-1' and S-2' subsites was studied using two libraries of pseudotripeptides containing the S-1 synthon derived from the best beta-amino thiol tested. Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a K-i value of 20 nM.

  DOI：

  10.1021/jm0300680

文献信息

• Development of Potent Inhibitors of Botulinum Neurotoxin Type B
  作者：Christine Anne、Serge Turcaud、Jean Quancard、Franck Teffo、Hervé Meudal、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm0300680

  日期：2003.10.1

  Botulinum neurotoxins are the most potent toxins known to date. They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis. There is a great interest in designing antagonists of the action of these toxins. One way is to inhibit their catalytic activity. In this study, we report the design of such inhibitors directed toward BoNT/B. A study of the S-1 subsite specificity, using several beta-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety. The specificity of the S-1' and S-2' subsites was studied using two libraries of pseudotripeptides containing the S-1 synthon derived from the best beta-amino thiol tested. Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a K-i value of 20 nM.