通过激活的白素直接抽取原子:一个实验和计算研究
Andrea Decker1, Marina S Chow, Jyllian N Kemsley
1Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Journal of the American Chemical Society
|April 6, 2006
概括
活性白素 (ABLM) 直接从DNA中抽取原子,这是其破坏DNA的化疗机制的关键步骤. 这一发现澄清了白素 (BLM) 的作用及其在双链DNA裂变中的作用.
科学领域:
- 生物化学 生物化学
- 化学生物学 化学生物学
- 分子生物学分子生物学
背景情况:
- 白素 (BLM) 是一种已知会导致DNA损伤的化疗剂.
- 活性白素 (ABLM),一种Fe (III) -OOH复合物,通过原子抽象参与DNA裂变.
- ABLM的DNA攻击的确切机制和活跃物种仍然不清楚.
研究的目的:
- 为了研究活性白素 (ABLM) 的反应性.
- 阐明ABLM对DNA最初攻击的机制.
- 为了确定BLM诱导的DNA损伤中活性氧化物种的性质.
主要方法:
- 动力测量使用循环二重化谱学来监测ABLM反应.
- 同位素效应研究 (kH/kD ≈3) 探测速度决定步骤.
- 密度函数计算用于评估潜在能量表面的H原子抽象.
主要成果:
- 实验证据表明ABLM经历了原子抽象,由H原子捐赠者加速.
- 动态同位素效应表明原子参与了限制速度的步骤.
- 密度函数计算支持ABLM的直接H原子抽象,因为它在热力学和动力学上优于O-O键裂解.
结论:
- ABLM直接从DNA的脱氧化4'-H中提取原子.
- 这种H原子抽象产生了反应性Fe(IV) = O物种,解释了观察到的双链DNA裂变.
- 这项研究提供了对白胺的DNA损伤途径的机械洞察.
相关概念视频
Subatomic Particles
Dalton was only partially correct about the particles that make up matter. All matter is composed of atoms, and atoms are composed of three smaller subatomic particles: protons, neutrons, and electrons. These three particles account for the mass and the charge of an atom.
Nuclear Transmutation
Nuclear transmutation is the conversion of one nuclide into another. It can occur by the radioactive decay of a nucleus, or the reaction of a nucleus with another particle. The first manmade nucleus was produced in Ernest Rutherford’s laboratory in 1919 by a transmutation reaction, the bombardment of one type of nuclei with other nuclei or with neutrons. Rutherford bombarded nitrogen-14 atoms with high-speed α particles from a natural radioactive isotope of radium and observed protons being...
Electron Behavior
Electrons are negatively charged subatomic particles attracted to and orbit around the positively-charged nucleus of an atom. They reside in spaces associated with energy levels called shells and are further organized into subshells and orbitals within each shell.
Electrons Orbit the Nucleus
Electrons are found in specific locations outside of the nucleus. The shell in which an electron resides indicates the general energy level of the electron: those closer to the nucleus have less energy,...
Electrons Orbit the Nucleus
Electrons are found in specific locations outside of the nucleus. The shell in which an electron resides indicates the general energy level of the electron: those closer to the nucleus have less energy,...
Thomson's e/m Experiment
In a beam of charged particles created by a heated cathode, the particles move at different speeds. However, many applications need a beam with uniform particle speeds. An arrangement known as a velocity selector uses electric and magnetic fields to pick particles with a particular speed from the beam.
A particle with charge q, speed v, and mass m enters an area from the top, where the magnetic and electric fields are perpendicular both to the particle's motion and to one another. The magnetic...
A particle with charge q, speed v, and mass m enters an area from the top, where the magnetic and electric fields are perpendicular both to the particle's motion and to one another. The magnetic...
Atomic Absorption Spectroscopy: Atomization Methods
Atomic Absorption Spectroscopy (AAS) atomizes samples through flame atomization or electrothermal atomization. Flame atomization typically involves a nebulizer and spray chamber assembly to combine the sample with a fuel–oxidant mixture, creating a fine aerosol mist that enters a burner. Typically, the fuel and oxidant are combined in an approximately stoichiometric ratio. However, for atoms that are easily oxidized, a fuel-rich mixture may be more advantageous. Only about 5% of the aerosol...


