4-Hydroxynon-2-en-8-ynal | 1011268-23-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-Hydroxynon-2-en-8-ynal
• CAS: 1011268-23-7
• 化学式: C₉H₁₂O₂
• 分子量: 152.193
• InChiKey: RXECVCDYORIBBT-UHFFFAOYSA-N

物化性质

• 沸点：
  292.3±40.0 °C(Predicted)
• 密度：
  1.016±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：2.5mg/mL； DMSO：2mg/mL；乙醇：12.5mg/mL； PBS（pH 7.2）：5 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-庚炔-1-醇 在 哌啶 、 sodium hydride 、 二异丁基氢化铝 、 乙二胺 、 pyridinium chlorochromate 作用下， 以 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 生成 4-Hydroxynon-2-en-8-ynal
  参考文献：
  名称：

  Temporally Controlled Targeting of 4-Hydroxynonenal to Specific Proteins in Living Cells

  摘要：

  In-depth chemical understanding of complex biological processes hinges upon the ability to systematically perturb individual systems. However, current approaches to study impacts of biologically relevant reactive small molecules involve bathing of the entire cell or isolated organelle with excess amounts, leading to off-target effects. The resultant lack of biochemical specificity has plagued our understanding of how biological electrophiles mediate signal transduction or regulate responses that confer defense mechanisms to cellular electrophilic stress Here we introduce a target specific electrophile delivery platform that will ultimately pave the way to interrogate effects of reactive electrophiles on specific target proteins in cells. The new methodology is demonstrated by photoinducible targeted delivery of 4-hydroxynonenal (HNE) to the proteins Keap1 and PTEN. Covalent conjugation of the HNE-precursor to HaloTag fused to the target proteins enables directed HNE delivery upon photoactivation. The strategy provides proof of concept of selective delivery of reactive electrophiles to individual electrophile-responsive proteins in mammalian cells. It opens a new avenue enabling more precise determination of the pathophysiological consequences of HNE-induced chemical modifications on specific target proteins in cells.

  DOI：

  10.1021/ja405400k

文献信息

• A Generalizable Platform for Interrogating Target- and Signal-Specific Consequences of Electrophilic Modifications in Redox-Dependent Cell Signaling
  作者：Hong-Yu Lin、Joseph A. Haegele、Michael T. Disare、Qishan Lin、Yimon Aye

  DOI：10.1021/ja5132648

  日期：2015.5.20

  Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1),constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling These data Show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keapl protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keapl as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-inolecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.
• Temporally Controlled Targeting of 4-Hydroxynonenal to Specific Proteins in Living Cells
  作者：Xinqiang Fang、Yuan Fu、Marcus J. C. Long、Joseph A. Haegele、Eva J. Ge、Saba Parvez、Yimon Aye

  DOI：10.1021/ja405400k

  日期：2013.10.2

  In-depth chemical understanding of complex biological processes hinges upon the ability to systematically perturb individual systems. However, current approaches to study impacts of biologically relevant reactive small molecules involve bathing of the entire cell or isolated organelle with excess amounts, leading to off-target effects. The resultant lack of biochemical specificity has plagued our understanding of how biological electrophiles mediate signal transduction or regulate responses that confer defense mechanisms to cellular electrophilic stress Here we introduce a target specific electrophile delivery platform that will ultimately pave the way to interrogate effects of reactive electrophiles on specific target proteins in cells. The new methodology is demonstrated by photoinducible targeted delivery of 4-hydroxynonenal (HNE) to the proteins Keap1 and PTEN. Covalent conjugation of the HNE-precursor to HaloTag fused to the target proteins enables directed HNE delivery upon photoactivation. The strategy provides proof of concept of selective delivery of reactive electrophiles to individual electrophile-responsive proteins in mammalian cells. It opens a new avenue enabling more precise determination of the pathophysiological consequences of HNE-induced chemical modifications on specific target proteins in cells.