通过fasicularin引起的DNA损伤
Sanjay Dutta1, Hideki Abe, Sakae Aoyagi
1School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Journal of the American Chemical Society
|October 27, 2005
概括
法西库拉林 (fasicularin) 是一种来自海的新型化物,通过化瓜残留物破坏DNA. 这种天然化合物形成了类似于某些化疗药物的阿齐里迪尼离子,为破坏DNA的天然产品提供了新的见解.
科学领域:
- 自然产品化学 自然产品化学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 法西库拉林是一种新型含有硫酸的化物,从草中分离出来 *Nephteis fasicularis*.
- 之前的研究表明,法西库拉林具有细胞毒性,可能是通过DNA损伤.
研究的目的:
- 阐明法西古拉林诱导DNA损伤的机制.
- 为了描述参与fasicularin介导的DNA裂变的化学物种.
主要方法:
- 用fasicularin处理的5'-32P标记的DNA复合体的序列凝分析.
- 生物化学测试以确定DNA病变和反应性中间体.
主要成果:
- 法西古拉林治疗导致DNA中的瓜残留物选择性链裂变.
- 该DNA损伤机制涉及氨酸化由一个fasicularin衍生的亚齐里迪尼离子.
- 这种阿齐里丁离子形成类似于临床上使用的抗癌化剂.
结论:
- 法西库拉林是第一个被发现能产生DNA化阿齐里迪尼离子的天然产品.
- 法西库拉林的作用机制为DNA化提供了一种与抗癌药物开发相关的新型天然产品模型.
相关概念视频
Nucleotide Excision Repair
Overview
Mutations
Overview
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...


