PHOTOCHEMISTRY OF DNA NUCLEOBASES AND RELATED COMPOUNDS

DNA 核碱基及相关化合物的光化学

• 批准号: 8169742
• 负责人: MARTIN D SHETLAR
• 金额: $ 0.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169742
• 关键词: Amino Acids; Bromouracil; Carbon; Cell Death; Cells; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Cytosine; DNA; DNA Damage; Digestion; Electrospray Ionization; Environment; Funding; Gene Mutation; Genomics; Grant; High Pressure Liquid Chromatography; Institution; Investigation; Life; Light; Mass Spectrum Analysis; Mediating; Minor; NMR Spectroscopy; Nucleosides; Photochemistry; Procedures; Proteins; Protons; Research; Research Personnel; Resources; Role; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrum Analysis; Thymine; UV induced; Ultraviolet Rays; United States National Institutes of Health; Uracil; Water; Work; absorption; adduct; base; chemical stability; interest; metaplastic cell transformation; nucleobase; ultraviolet

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ultraviolet (UV) light is known to cause a number of effects after absorption by living cells, such as genetic mutation, cell death and cellular transformation. These latter types of damage are mediated, at least in part, by photoproducts formed in the genomic DNA of the cell. One main focus of our work is on the role of the minor base 5-methylcytosine (m5C) in mediating damage induced by absorption of light, although investigations of the reactivity of thymine (Thy), cytosine (Cyt) and halogenated uracils (e.g. 5-bromouracil) are also being carried out. Our primary aim is directed towards isolating and characterizing a number of photoproducts that we believe could be relevant to achieving a chemical understanding of UV-induced DNA damage. Among the compounds of current interest are the (6-4) adducts and Dewar adducts of m5C with Cyt and Thy, both in nucleobase and nucleoside form and on adducts formed with molecules in the environment of DNA in the cell (e.g. water, amino acids in proteins). These compounds are being prepared utilizing procedures that avoid conditions under which these compounds are unstable. High performance liquid chromatography (HPLC) is being used to isolate the various compounds in a pure state. They are being structurally characterized using proton and carbon-13 NMR spectroscopy, UV spectroscopy, electrospray ionization and MALDI mass spectrometry and, where appropriate, circular dichroic spectroscopy. Their chemical stability under conditions of DNA digestion is also being determined.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 已知紫外线（紫外线）的光在活细胞吸收后引起许多影响，例如遗传突变，细胞死亡和细胞转化。 这些后一种类型的损伤至少部分是由细胞基因组DNA中形成的光产物介导的。我们工作的一个主要重点是次要基碱5-甲基胞嘧啶（M5C）在吸收光引起的损害中的作用，尽管对胸腺嘧啶（THY），胞嘧啶（CYT）的反应性研究的研究也被带出了（例如5-溴）。 我们的主要目的是旨在隔离和表征许多我们认为可能与对紫外线诱导的DNA损伤的化学理解有关的光产物。 当前感兴趣的化合物中有M5C的（6-4）加合物和杜瓦加合物与Cyt和Thy的（在核碱基和核苷形式中，以及在细胞中DNA环境中形成的分子形成的加合物（例如，蛋白质中的氨基酸，氨基酸）。 这些化合物正在采用避免这些化合物不稳定的条件的过程制备。 高性能液相色谱法（HPLC）用于隔离纯状态的各种化合物。 它们在结构上使用质子和碳-13 NMR光谱，紫外光谱，电喷雾电离和MALDI质谱法以及适当的圆形二分色谱法。在DNA消化条件下，它们的化学稳定性也得到了确定。