(5-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-2,4-dinitrophenyl)-L-aspartic acid | 199730-00-2

• 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: (5-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-2,4-dinitrophenyl)-L-aspartic acid
• CAS: 199730-00-2
• 化学式: C₁₆H₂₁N₅O₉
• 分子量: 427.371
• InChiKey: JZPWVTLWSTULDG-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.15
• 重原子数：
  30.0
• 可旋转键数：
  12.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  228.03
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  L-天门冬氨酸 、 D,L-FDLA 在 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 (5-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-2,4-dinitrophenyl)-L-aspartic acid 、
  参考文献：
  名称：

  Fuscasins AD，来自海洋海绵Phakellia fusca的环肽肽。

  摘要：

  从南海采集的海生海绵Phakellia fusca中分离出四个新的环七肽，fuscasins AD（1-4）。它们的平面结构已通过分光光度法进行了充分表征，并使用先进的Marfey法确定了氨基酸残基的绝对构型。在结构上，1是独特的环庚肽，其主链带有吡咯烷-2,5-二酮单元。在分离出的化合物中，有1种对HepG2细胞表现出有效的生长抑制活性，IC50值为4.6μM，而对其他五种人类癌细胞系MCF-7，HeLa，NCI-H460， PC9和SW480。令人鼓舞的是，即使浓度高达100μM，1也没有表现出对非恶性细胞的细胞毒性。

  DOI：

  10.1021/acs.jnatprod.8b01033

文献信息

• Expanded Sequence Space of Radical S‐Adenosylmethionine‐Dependent Enzymes Involved in Post‐translational Macrocyclization**
  作者：Bei‐Bei He、Zhuo Cheng、Zheng Zhong、Ying Gao、Hongyan Liu、Yong‐Xin Li

  DOI：10.1002/anie.202212447

  日期：2022.11.25

  The rSAM enzymes are known to catalyze diverse crosslink formation in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). Here, we develop a small peptide and enzyme co-occurrence analysis workflow (SPECO) to reveal the untapped biosynthetic landscape of rSAM-modified RiPPs and characterize cyclophane-forming enzymes that catalyze various tyrosine/histidine-aliphatic

  已知 rSAM 酶在核糖体合成和翻译后修饰的肽 (RiPP) 的生物合成中催化不同的交联形成。在这里，我们开发了一个小肽和酶共现分析工作流程 (SPECO)，以揭示 rSAM 修饰的 RiPP 尚未开发的生物合成景观，并表征催化各种酪氨酸/组氨酸-脂肪族侧链交联的环状烷形成酶。
• Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities
  作者：Cheng Wang、Leonhard M. Henkes、Leah B. Doughty、Min He、Difei Wang、Franz-Josef Meyer-Almes、Yi-Qiang Cheng

  DOI：10.1021/np200324x

  日期：2011.10.28

  Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI(50) for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development.