(S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-3-phenylpropanoic acid | 148333-47-5

• 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: (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-3-phenylpropanoic acid
• 英文别名: Ac-Leu-Val-Phe-OH；(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoic acid
• CAS: 148333-47-5
• 化学式: C₂₂H₃₃N₃O₅
• 分子量: 419.521
• InChiKey: VZVCTEYKALYRIE-FHWLQOOXSA-N

物化性质

• 沸点：
  729.5±60.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-3-phenylpropanoic acid 在 N-甲基哌啶 、 氢溴酸 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 生成 3(S)-<<(acetyl-(S)-leucinyl)-(S)-valinyl>amino>-1-bromo-4-phenylbutan-2-one
  参考文献：
  名称：

  Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.

  摘要：

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.

  DOI：

  10.1021/ja00146a007
• 作为产物：
  描述：

  methyl (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-3-phenylpropanoate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以95%的产率得到(S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-3-phenylpropanoic acid
  参考文献：
  名称：

  Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.

  摘要：

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.

  DOI：

  10.1021/ja00146a007

文献信息

• [EN] HIV PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEASE DU VIH
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：WO1996016950A1

  公开（公告）日：1996-06-06

  (EN) A HIV-1 protease inhibitor which includes an N-terminal cycle (A) or a C-terminal cycle (B) or both cycles (A) and (B) wherein Y is selected from side chains of Asn or Ile or Val or Glu and alkyl of 1-6 carbon atoms inclusive of linear or branched chains as well as cycloalkyl; and X is selected from (CH2)n where n = 3-6, -CH(OH)-CH(OH)-CH2-, CH(CO2H)-CH2-CH2, CH2CONHCHR where R = D or L amino acids and alkyl of 1-6 carbon atoms inclusive of linear or branched chains.(FR) L'invention concerne un inhibiteur de la protéase du VIH-1 comprenant un cycle N-terminal ayant la formule (A) ou un cycle C-terminal ayant la formule (B), ou encore les deux. Dans ces formules, Y est choisi parmi des chaînes latérales d'Asn, d'Ile, de Val ou de Glu et alkyle à 1-6 atomes de carbone linéaire, ramifié ou cyclique, X est choisi parmi (CH2)n, où n = 3-6, -CH(OH)-CH(OH)-CH2-, CH(CO2H)-CH2-CH2, CH2CONHCHR où R est un acide aminé D ou L ou un alkyle à 1-6 atomes de carbone linéaire ou ramifié.

  一种 HIV-1 蛋白酶抑制剂，包含 N端循环（A）或 C端循环（B）或两者，其中 Y 是丝氨酸、色氨酸、丙氨酸或谷氨酸的侧链，选自 1-6 个碳原子的烷基（包括直链、分支链或环烷基）；X 是选自（CH2)n（此处，n = 3-6），-CH(OH)-CH(OH)-CH2-，CH(CO2H)-CH2-CH2，CH2CONHCHR，其中 R 是 L 或 D 赝氨酸以及 1-6 个碳原子的烷基（直链或分支链）。
• US6043357A
  申请人：——

  公开号：US6043357A

  公开（公告）日：2000-03-28
• Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.
  作者：G. Abbenante、D. R. March、D. A. Bergman、P. A. Hunt、B. Garnham、R. J. Dancer、J. L. Martin、D. P. Fairlie

  DOI：10.1021/ja00146a007

  日期：1995.10

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.