((Boc-Lys(Boc))2Lys)2Lys-Ser(OtBu)-Gln(NHTrt)-Asn(NHTrt)-Tyr(OtBu)-Pro-Ile-Val-Phe-OH | 1262241-41-7

• 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: ((Boc-Lys(Boc))2Lys)2Lys-Ser(OtBu)-Gln(NHTrt)-Asn(NHTrt)-Tyr(OtBu)-Pro-Ile-Val-Phe-OH
• CAS: 1262241-41-7
• 化学式: C₁₇₄H₂₅₈N₂₄O₃₆
• 分子量: 3262.1
• InChiKey: ZHLHZTAKZBHQFX-IUYUFNFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  19.69
• 重原子数：
  234.0
• 可旋转键数：
  87.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  819.21
• 氢给体数：
  24.0
• 氢受体数：
  35.0

反应信息

• 作为反应物：
  描述：

  ((Boc-Lys(Boc))2Lys)2Lys-Ser(OtBu)-Gln(NHTrt)-Asn(NHTrt)-Tyr(OtBu)-Pro-Ile-Val-Phe-OH 、 (S)-2-amino-4-methyl-N-(4-methyl-2-oxo-2H-chromen-7-yl)pentanamide 2,2,2-trifluoroacetate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以26.3 mg的产率得到
  参考文献：
  名称：

  HIV Protease-Mediated Activation of Sterically Capped Proteasome Inhibitors and Substrates

  摘要：

  Strategies for selectively killing HIV-infected cells present an appealing alternative to traditional antiretroviral drugs. We show here the first example of an inactive "Trojan horse" molecule that releases a cytotoxic, small-molecule proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept strategy, the protein avidin was used to block entry of the compound into the proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is also feasible without requiring an exogenous protein; a polylysine dendrimer-containing molecule is unable to enter the proteasome until cleaved by HIV-1 protease. These results demonstrate that conditional proteasome inhibitors could prove useful in the development of new tools for chemical biology and future therapeutics.

  DOI：

  10.1021/ja109377p
• 作为产物：
  描述：

  Fmoc-phenylalanine-2-chlorotrityl resin 、 Fmoc-L-缬氨酸 、 Fmoc-L-脯氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-L-异亮氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 Fmoc-N-三苯甲基-L-谷氨酰胺 、 (Boc-Lys(Boc))2Lys-OH 在 哌啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 ((Boc-Lys(Boc))2Lys)2Lys-Ser(OtBu)-Gln(NHTrt)-Asn(NHTrt)-Tyr(OtBu)-Pro-Ile-Val-Phe-OH
  参考文献：
  名称：

  HIV Protease-Mediated Activation of Sterically Capped Proteasome Inhibitors and Substrates

  摘要：

  Strategies for selectively killing HIV-infected cells present an appealing alternative to traditional antiretroviral drugs. We show here the first example of an inactive "Trojan horse" molecule that releases a cytotoxic, small-molecule proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept strategy, the protein avidin was used to block entry of the compound into the proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is also feasible without requiring an exogenous protein; a polylysine dendrimer-containing molecule is unable to enter the proteasome until cleaved by HIV-1 protease. These results demonstrate that conditional proteasome inhibitors could prove useful in the development of new tools for chemical biology and future therapeutics.

  DOI：

  10.1021/ja109377p