Ac-ARA-OCH3 | 1235442-37-1

• 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: Ac-ARA-OCH3
• 英文别名: Ac-ARA-COOCH3；methyl (2S)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoate
• CAS: 1235442-37-1
• 化学式: C₁₅H₂₈N₆O₅
• 分子量: 372.425
• InChiKey: VXMGKWGBQTWNEN-QXEWZRGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  178
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甲醇 、 在 三氟乙酸 、 水 、 1,4-二巯基-2,3-丁二醇 作用下， 反应 72.0h， 生成 Ac-ARA-OCH3
  参考文献：
  名称：

  Analysis of the Binding of Mixed Lineage Leukemia 1 (MLL1) and Histone 3 Peptides to WD Repeat Domain 5 (WDR5) for the Design of Inhibitors of the MLL1−WDR5 Interaction

  摘要：

  MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methyltransferase activity of MLL1 and targeting this interaction using small molecules may represent an attractive therapeutic strategy. In this study, we have defined the essential elements in MLL1 required for its high-affinity binding to WDR5. Our data showed that the minimal elements crucial for high-affinity binding of MLL1 to WDR5 are -CO-ARA-NH- motif and two intramolecular hydrogen bonds that stabilize the conformation of this motif. Two 3-mer peptides, Ac-ARA-NH(2) and Ac-ART-NH(2), were designed based upon MLL1 and H3 sequences and achieved K(i) values of 120 and 20 nM to WDR5, respectively. Our study provides a concrete basis for the design of potent peptidomimetics and nonpeptidic compounds to inhibit MLL1 activity by targeting the MLL1 and WDR5 interaction.

  DOI：

  10.1021/jm100139b

文献信息

• Analysis of the Binding of Mixed Lineage Leukemia 1 (MLL1) and Histone 3 Peptides to WD Repeat Domain 5 (WDR5) for the Design of Inhibitors of the MLL1−WDR5 Interaction
  作者：Hacer Karatas、Elizabeth C. Townsend、Denzil Bernard、Yali Dou、Shaomeng Wang

  DOI：10.1021/jm100139b

  日期：2010.7.22

  MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methyltransferase activity of MLL1 and targeting this interaction using small molecules may represent an attractive therapeutic strategy. In this study, we have defined the essential elements in MLL1 required for its high-affinity binding to WDR5. Our data showed that the minimal elements crucial for high-affinity binding of MLL1 to WDR5 are -CO-ARA-NH- motif and two intramolecular hydrogen bonds that stabilize the conformation of this motif. Two 3-mer peptides, Ac-ARA-NH(2) and Ac-ART-NH(2), were designed based upon MLL1 and H3 sequences and achieved K(i) values of 120 and 20 nM to WDR5, respectively. Our study provides a concrete basis for the design of potent peptidomimetics and nonpeptidic compounds to inhibit MLL1 activity by targeting the MLL1 and WDR5 interaction.