4-((4-(di-tert-butylfluorosilyl)phenethyl)amino)-2,3-dihydroxy-4-oxobutanoyl-Arg-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH₂

• 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-((4-(di-tert-butylfluorosilyl)phenethyl)amino)-2,3-dihydroxy-4-oxobutanoyl-Arg-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH₂
• 英文别名: (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[5-[[(2S)-5-(diaminomethylideneamino)-2-[[4-[2-[4-[ditert-butyl(fluoro)silyl]phenyl]ethylamino]-2,3-dihydroxy-4-oxobutanoyl]amino]pentanoyl]amino]pentanoylamino]pentanediamide
• 化学式: C₇₈H₁₂₄FN₁₉O₁₆Si
• 分子量: 1631.04
• InChiKey: AQPACODANBKUNA-HCHDHZEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.57
• 重原子数：
  115
• 可旋转键数：
  50
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  567
• 氢给体数：
  19
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 、 、 2,3-diacetoxy-4-(4-(di-tert-butylfluorosilyl)phenethylamino)-4-oxobutanoic acid 、 5-[[芴甲氧羰基]氨基]戊酸 、 芴甲氧羰酰基肌氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.58h， 生成 4-((4-(di-tert-butylfluorosilyl)phenethyl)amino)-2,3-dihydroxy-4-oxobutanoyl-Arg-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH₂
  参考文献：
  名称：

  Studies toward the Development of New Silicon-Containing Building Blocks for the Direct ¹⁸F-Labeling of Peptides

  摘要：

  Silicon-containing prosthetic groups have been conjugated to peptides to allow for a single-step labeling with F-18 radioisotope. The fairly lipophilic di-tert-butylphenylsilane building block contributes unfavorably to the pharmacokinetic profile of bombesin conjugates. In this article, theoretical and experimental studies toward the development of more hydrophilic silicon-based building blocks are presented. Density functional theory calculations were used to predict the hydrolytic stability of di-tert-butylfluorosilanes 2-23 with the aim to improve the in vivo properties of F-18-labeled silicon-containing biomolecules. As a further step toward improving the pharmacokinetic profile, hydrophilic linkers were introduced between the lipophilic di-tert-butylphenylsilane building block and the bombesin congeners. Increased tumor uptake was shown with two of these peptides in xenograft-bearing mice using positron emission tomography and biodistribution studies. The introduction of a hydrophilic linker is thus a viable approach to improve the tumor uptake of F-18-labeled silicon bombesin conjugates.

  DOI：

  10.1021/jm400857f