2-[(2S,5R,8S,11S)-5-benzyl-8-[[1-[3-[(3S,6S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-2,5,9,12-tetraoxo-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-en-6-yl]propyl]triazol-4-yl]methyl]-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;2,2,2-trifluoroacetic acid | 1424402-73-2

• 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: 2-[(2S,5R,8S,11S)-5-benzyl-8-[[1-[3-[(3S,6S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-2,5,9,12-tetraoxo-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-en-6-yl]propyl]triazol-4-yl]methyl]-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;2,2,2-trifluoroacetic acid
• CAS: 1424402-73-2
• 化学式: C₂HF₃O₂*C₆₃H₈₀ClN₁₃O₁₅
• 分子量: 1408.88
• InChiKey: JGMHWPQHIKJHSX-PFDQKBNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  99
• 可旋转键数：
  22
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  448
• 氢给体数：
  11
• 氢受体数：
  23

反应信息

• 作为产物：
  描述：

  cyclo[Arg-Gly-Asp-D-Phe-Pra] 、 (3S,6S,10R,13E,16S)-6-(3-azidopropyl)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone 、 三氟乙酸 在 铜 作用下， 以 水 、 叔丁醇 为溶剂， 以68%的产率得到2-[(2S,5R,8S,11S)-5-benzyl-8-[[1-[3-[(3S,6S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-2,5,9,12-tetraoxo-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-en-6-yl]propyl]triazol-4-yl]methyl]-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis

  摘要：

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

  DOI：

  10.1021/jm301346z

文献信息

• Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
  作者：Markus Nahrwold、Christine Weiß、Tobias Bogner、Felix Mertink、Jens Conradi、Benedikt Sammet、Ralf Palmisano、Soledad Royo Gracia、Thomas Preuße、Norbert Sewald

  DOI：10.1021/jm301346z

  日期：2013.3.14

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.