(S)-4-[(3,5-bis-trifluoromethylbenzyl)tert-butoxycarbonylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid | 938464-88-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-4-[(3,5-bis-trifluoromethylbenzyl)tert-butoxycarbonylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid
• 英文别名: (2S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoic acid
• CAS: 938464-88-1
• 化学式: C₃₃H₃₂F₆N₂O₆
• 分子量: 666.617
• InChiKey: WJDBBXHBIZLJLV-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-4-[(3,5-bis-trifluoromethylbenzyl)tert-butoxycarbonylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid 、 Fmoc-L-丙氨酸 、 Fmoc-O-叔丁基-L-谷氨酸 、 Fmoc-Pbf-L-精氨酸 以15%的产率得到
  参考文献：
  名称：

  Polyfluorinated Amino Acids for Sensitive ¹⁹F NMR-Based Screening and Kinetic Measurements

  摘要：

  Two novel series of polyfluorinated amino acids (PFAs) were designed and synthesized according to a very short and scalable synthetic sequence. The advantages and limitations of these moieties for screening purposes are presented and discussed. The potential applications of these PFAs were tested with their incorporation into small arginine-containing peptides that represent suitable substrates for the enzyme trypsin. The enzymatic reactions were monitored by F-19 NMR spectroscopy, using the 3-FABS (three fluorine atoms for biochemical screening) technique. The high sensitivity achieved with these PFAs permits a reduction in substrate concentration required for 3-FABS. This is relevant in the utilization of 3-FABS in fragment-based screening for identification of small scaffolds that bind weakly to the receptor of interest. The large dispersion of F-19 isotropic chemical shifts allows the simultaneous measurement of the efficiency of the different substrates, thus identifying the best substrate for screening purposes. Furthermore, the knowledge of K-M and K-cat for the different substrates allows the identification of the structural motifs responsible for the binding affinity to the receptor and those affecting the chemical steps in enzymatic catalysis. This enables the construction of suitable pharmacophores that can be used for designing nonpeptidic inhibitors with high affinity for the enzyme or molecules that mimic the transition state. The novel PFAs can also find useful application in the FAXS (fluorine chemical shift anisotropy and exchange for screening) experiment, a F-19-based competition binding assay for the detection of molecules that inhibit the interaction between two proteins.

  DOI：

  10.1021/ja069128s
• 作为产物：
  描述：

  Fmoc-L-谷氨酰胺 在 吡啶 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 三氟乙酸 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (S)-4-[(3,5-bis-trifluoromethylbenzyl)tert-butoxycarbonylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid
  参考文献：
  名称：

  Polyfluorinated Amino Acids for Sensitive ¹⁹F NMR-Based Screening and Kinetic Measurements

  摘要：

  Two novel series of polyfluorinated amino acids (PFAs) were designed and synthesized according to a very short and scalable synthetic sequence. The advantages and limitations of these moieties for screening purposes are presented and discussed. The potential applications of these PFAs were tested with their incorporation into small arginine-containing peptides that represent suitable substrates for the enzyme trypsin. The enzymatic reactions were monitored by F-19 NMR spectroscopy, using the 3-FABS (three fluorine atoms for biochemical screening) technique. The high sensitivity achieved with these PFAs permits a reduction in substrate concentration required for 3-FABS. This is relevant in the utilization of 3-FABS in fragment-based screening for identification of small scaffolds that bind weakly to the receptor of interest. The large dispersion of F-19 isotropic chemical shifts allows the simultaneous measurement of the efficiency of the different substrates, thus identifying the best substrate for screening purposes. Furthermore, the knowledge of K-M and K-cat for the different substrates allows the identification of the structural motifs responsible for the binding affinity to the receptor and those affecting the chemical steps in enzymatic catalysis. This enables the construction of suitable pharmacophores that can be used for designing nonpeptidic inhibitors with high affinity for the enzyme or molecules that mimic the transition state. The novel PFAs can also find useful application in the FAXS (fluorine chemical shift anisotropy and exchange for screening) experiment, a F-19-based competition binding assay for the detection of molecules that inhibit the interaction between two proteins.

  DOI：

  10.1021/ja069128s

文献信息

• Fluorinated amino acids and peptides
  申请人：NERVIANO MEDICAL SCIENCES S.r.l.

  公开号：EP1923397B1

  公开（公告）日：2009-10-28
• Polyfluorinated Amino Acids for Sensitive ¹⁹F NMR-Based Screening and Kinetic Measurements
  作者：Gianluca Papeo、Patrizia Giordano、Maria Gabriella Brasca、Ferdinando Buzzo、Dannica Caronni、Franco Ciprandi、Nicola Mongelli、Marina Veronesi、Anna Vulpetti、Claudio Dalvit

  DOI：10.1021/ja069128s

  日期：2007.5.1

  Two novel series of polyfluorinated amino acids (PFAs) were designed and synthesized according to a very short and scalable synthetic sequence. The advantages and limitations of these moieties for screening purposes are presented and discussed. The potential applications of these PFAs were tested with their incorporation into small arginine-containing peptides that represent suitable substrates for the enzyme trypsin. The enzymatic reactions were monitored by F-19 NMR spectroscopy, using the 3-FABS (three fluorine atoms for biochemical screening) technique. The high sensitivity achieved with these PFAs permits a reduction in substrate concentration required for 3-FABS. This is relevant in the utilization of 3-FABS in fragment-based screening for identification of small scaffolds that bind weakly to the receptor of interest. The large dispersion of F-19 isotropic chemical shifts allows the simultaneous measurement of the efficiency of the different substrates, thus identifying the best substrate for screening purposes. Furthermore, the knowledge of K-M and K-cat for the different substrates allows the identification of the structural motifs responsible for the binding affinity to the receptor and those affecting the chemical steps in enzymatic catalysis. This enables the construction of suitable pharmacophores that can be used for designing nonpeptidic inhibitors with high affinity for the enzyme or molecules that mimic the transition state. The novel PFAs can also find useful application in the FAXS (fluorine chemical shift anisotropy and exchange for screening) experiment, a F-19-based competition binding assay for the detection of molecules that inhibit the interaction between two proteins.