cyclo(pTyr-Acp-Asn-Val-Cys-CH2CO) | 1163708-16-4

• 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: cyclo(pTyr-Acp-Asn-Val-Cys-CH2CO)
• 英文别名: 4-{[(9S,15R,18S,21S)-15-carbamoyl-21-(carbamoylmethyl)-8,11,17,20,23-pentaoxo-18-(propan-2-yl)-13-thia-2,7,10,16,19,22-hexaazaspiro[5.17]tricosan-9-yl]methyl}phenoxyphosphonic acid；[4-[[(9S,15R,18S,21S)-21-(2-amino-2-oxoethyl)-15-carbamoyl-8,11,17,20,23-pentaoxo-18-propan-2-yl-13-thia-2,7,10,16,19,22-hexazaspiro[5.17]tricosan-9-yl]methyl]phenyl] dihydrogen phosphate
• CAS: 1163708-16-4
• 化学式: C₂₉H₄₃N₈O₁₁PS
• 分子量: 742.747
• InChiKey: HIOLSTZWHFWABX-LZIFKYDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  336
• 氢给体数：
  10
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  溴代乙酸酐 、 N-[4-(1-芘基)丁酰基]甘氨酸 、 3-{[(9H-芴-9-基甲氧基)羰基]氨基}-3-哌啶羧酸 、 Fmoc-L-缬氨酸 、 N-芴甲氧羰基-O-苄基-L-磷酸酪氨酸 、 Fmoc-L-天冬酰胺 在 哌啶 、 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 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 cyclo(pTyr-Acp-Asn-Val-Cys-CH2CO)
  参考文献：
  名称：

  Discovery of thioether-bridged cyclic pentapeptides binding to Grb2-SH2 domain with high affinity

  摘要：

  Blocking the interaction between phosphotyrosine (pTyr)-containing activated receptors and the Src homology 2 (SH2) domain of the growth factor receptor-bound protein 2 (Grb 2) is considered to be an effective and non-cytotoxic strategy to develop new anti-proliferate agents due to its potential to shut down the Ras activation pathway. In this study, a series of phosphotyrosine containing cyclic pentapeptides were designed and synthesized based upon the phage library derived cyclopeptide, G1TE. A comprehensive SAR study was also carried out to develop potent Grb2-SH2 domain antagonists based upon this novel template. With both the peptidomimetic optimization of the amino acid side-chains and the constraint of the backbone conformation guided by molecular modeling, we developed several potent antagonists with low micromolar range binding affinity, such as cyclic peptide 15 with an K(d) = 0.359 mu M, which is providing a novel template for the development of Grb2-SH2 domain antagonists as potential therapeutics for certain cancers. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.134