CHHNLTHAC | 1388146-05-1

• 英文名称: CHHNLTHAC
• CAS: 1388146-05-1
• 化学式: C₄₁H₆₂N₁₆O₁₂S₂
• 分子量: 1035.18
• InChiKey: PPWRRHKNLHJLLP-QIALRPDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.64
• 重原子数：
  71.0
• 可旋转键数：
  30.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  445.48
• 氢给体数：
  17.0
• 氢受体数：
  17.0

反应信息

• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-S-三苯甲基-L-半胱氨酸 、 Fmoc-O-叔丁基-L-苏氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 N-Fmoc-N'-三苯甲基-L-组氨酸 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， 生成 CHHNLTHAC
  参考文献：
  名称：

  Discovery of PTPRJ Agonist Peptides That Effectively Inhibit in Vitro Cancer Cell Proliferation and Tube Formation

  摘要：

  PTPRJ is a receptor protein tyrosine phosphatase involved in both physiological and oncogenic pathways. We previously reported that its expression is strongly reduced in the majority of explored cancer cell lines and tumor samples; moreover, its restoration blocks in vitro cancer cell proliferation and in vivo tumor formation. By means of a phage display library screening, we recently identified two peptides able to bind and activate PTPRJ, resulting in cell growth inhibition and apoptosis of both cancer and endothelial cells. Here, on a previously discovered PTPRJ agonist peptide, PTPRJ-pep19, we synthesized and assayed a panel of nonapeptide analogues with the aim to identify specific amino acid residues responsible for peptide activity. These second-generation nonapeptides were tested on both cancer and primary endothelial cells (HeLa and HUVEC, respectively); interestingly, one of them (PTPRJ-19.4) was able to both dramatically reduce cell proliferation and effectively trigger apoptosis of both HeLa and HVECs compared to its first-generation counterpart. Moreover, PTPRJ-pep19.4 significantly inhibited in vitro tube formation on Matrigel. Intriguingly, while ERK1/2 phosphorylation and cell proliferation were both inhibited by PTPRJ-pep 19.4 in breast cancer cells (MCF-7 and SKBr3), no effects were observed on primary normal human mammary endothelial cells (HMEC). We further characterized these peptides by molecular modeling and NMR experiments reporting, for the most active peptide, the possibility of self-aggregation states and highlighting new hints of structure-activity relationship. Thus, our results indicate that this nonapeptide might represent a great potential lead for the development of novel targeted anticancer drugs.

  DOI：

  10.1021/cb3007192