H-Thr-Ala-Tyr-Phe-Leu-Leu-aMeNva(vinyl)(vinyl)-Leu-Ala-Gly-aMeNva(vinyl)(vinyl)-Trp-NH2 | 1445137-63-2

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: H-Thr-Ala-Tyr-Phe-Leu-Leu-aMeNva(vinyl)(vinyl)-Leu-Ala-Gly-aMeNva(vinyl)(vinyl)-Trp-NH2
• 英文别名: (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-2-methylhept-6-enoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]acetyl]amino]-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-methylhept-6-enamide
• CAS: 1445137-63-2
• 化学式: C₇₅H₁₁₀N₁₄O₁₄
• 分子量: 1431.78
• InChiKey: PEYSMGDOGALVKB-ZTNHGPKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  103
• 可旋转键数：
  44
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  446
• 氢给体数：
  16
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  (2R)-2-N-芴甲氧羰基氨基-2-甲基-6-庚烯酸 、 Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-O-叔丁基-L-苏氨酸 、 Fmoc-L-色氨酸(Boc)-OH 在 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以34%的产率得到H-Thr-Ala-Tyr-Phe-Leu-Leu-aMeNva(vinyl)(vinyl)-Leu-Ala-Gly-aMeNva(vinyl)(vinyl)-Trp-NH2
  参考文献：
  名称：

  Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors

  摘要：

  HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the a-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their., helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or "nanoneedles" for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment.

  DOI：

  10.1021/jm4006516

文献信息

• Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors
  作者：Ya-Qiu Long、Shao-Xu Huang、Zahrah Zawahir、Zhong-Liang Xu、Huiyuan Li、Tino W. Sanchez、Ying Zhi、Stephanie De Houwer、Frauke Christ、Zeger Debyser、Nouri Neamati

  DOI：10.1021/jm4006516

  日期：2013.7.11

  HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the a-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their., helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or "nanoneedles" for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment.