Boc-Phe-Ψ[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2

• 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: Boc-Phe-Ψ[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2
• 英文别名: N-{(2R,3S)-3-[(tert-Butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-L-phenylalanyl-L-glutaminyl-L-phenylalaninamide；tert-butyl N-[(2S,3S)-4-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
• 化学式: C₃₈H₅₀N₆O₇
• 分子量: 702.851
• InChiKey: SSPOMXWWHDMCTH-XDIGFQIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  51
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  215
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  H-Phe-Gln(OBzL)-Phe-NH2 在 氢气 作用下， 生成 Boc-Phe-Ψ[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2
  参考文献：
  名称：

  Hydroxyethylamine Isostere of an HIV-1 Protease Inhibitor Prefers Its Amine to the Hydroxy Group in Binding to Catalytic Aspartates. A Synchrotron Study of HIV-1 Protease in Complex with a Peptidomimetic Inhibitor

  摘要：

  A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 Angstrom resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors. A comparison with another inhibitor of this series shows that the change of one atom of the P-2' side chain (Glu/Gln) leads to an altered ability of creating hydrogen bonds to the active site and within the inhibitor molecule. The diffraction data collected at a synchrotron radiation source enabled a detailed analysis of the complex solvation and of alternative conformations of protein side chains.

  DOI：

  10.1021/jm010979e

文献信息

• Hydroxyethylamine Isostere of an HIV-1 Protease Inhibitor Prefers Its Amine to the Hydroxy Group in Binding to Catalytic Aspartates. A Synchrotron Study of HIV-1 Protease in Complex with a Peptidomimetic Inhibitor
  作者：Jan Dohnálek、Jindřich Hašek、Jarmila Dušková、Hana Petroková、Martin Hradilek、Milan Souček、Jan Konvalinka、Jiří Brynda、Juraj Sedláček、Milan Fábry

  DOI：10.1021/jm010979e

  日期：2002.3.1

  A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 Angstrom resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors. A comparison with another inhibitor of this series shows that the change of one atom of the P-2' side chain (Glu/Gln) leads to an altered ability of creating hydrogen bonds to the active site and within the inhibitor molecule. The diffraction data collected at a synchrotron radiation source enabled a detailed analysis of the complex solvation and of alternative conformations of protein side chains.