Me-Ala-Val-Pro-Phe(Ph(3,4-diCl))-NH2.TFA | 1334727-05-7

• 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: Me-Ala-Val-Pro-Phe(Ph(3,4-diCl))-NH2.TFA
• 英文别名: (2S)-N-[(2S)-1-amino-3-[4-(3,4-dichlorophenyl)phenyl]-1-oxopropan-2-yl]-1-[(2S)-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid
• CAS: 1334727-05-7
• 化学式: C₂HF₃O₂*C₂₉H₃₇Cl₂N₅O₄
• 分子量: 704.574
• InChiKey: NQGBAJNLCNHJQU-WTKWDWFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.55
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  171
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  Fmoc-L-缬氨酸 、 BOC-N-甲基-L-丙氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-4-碘苯丙氨酸 、 3,4-二氯苯硼酸 、 三氟乙酸 在 N-乙基吗啉 、 Fmoc-Rink amide MBHA resin 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Me-Ala-Val-Pro-Phe(Ph(3,4-diCl))-NH2.TFA
  参考文献：
  名称：

  Solid-Phase Synthesis of Smac Peptidomimetics Incorporating Triazoloprolines and Biarylalanines

  摘要：

  Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural dues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide -alkyne c-ydoadditi on and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.

  DOI：

  10.1021/co200078u

文献信息

• Solid-Phase Synthesis of Smac Peptidomimetics Incorporating Triazoloprolines and Biarylalanines
  作者：Sebastian T. Le Quement、Mette Ishoey、Mette T. Petersen、Jacob Thastrup、Grith Hagel、Thomas E. Nielsen

  DOI：10.1021/co200078u

  日期：2011.11.14

  Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural dues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide -alkyne c-ydoadditi on and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.