REACTIVE INTERMEDIATES IN PHOTOCEMICAL REACTIONS OF BIOLOGICALLY RELEVANT PURINES

生物学相关嘌呤光化学反应中的反应中间体

• 批准号: 3936825
• 负责人: RAFAEL ARCE
• 金额: --
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3936825
• 关键词: adenine nucleotides; crosslink; dimer; electron spin resonance spectroscopy; flash photolysis; guanine nucleotides; nuclear magnetic resonance spectroscopy; nucleic acids; photochemistry; polynucleotides; purine nucleosides; purine nucleotides; pyrimidine nucleosides; pyrimidine nucleotides; radiation carcinogenesis; ultraviolet radiation

Ultraviolet radiation produces different types of lesions on DNA which unrepaired could lead to lethal, mutagenic and tumorigenic effects. In the last decade there have been reports on the formation of purine photoproducts in UV irradiated DNA which could lead to deleterious effects. Photochemical studies on monomeric purines and their derivatives from our laboratory indicate photodestruction yields as high as the one observed for monomeric pyrimidines. Also, the formation of highly reactive intermediates have been observed. These could initiate reaction with other bases and/or molecules close to the DNA. Our main objectives are: 1. To study and characterize the excited states and reactive intermediates participating in the photodestruction and photochemical reactions of purine deoxynucleotide dimers, oligo and polynucleotides. These will be characterized from their absorption spectra and kinetic behavior obtained with laser and conventional flash photolysis and fluorescence spectrometry. These studies will provide information on the mechanism of formation of the recently observed purine photoproducts in DNA. 2. Identify the stable products in the photodestruction of deoxyguanosine and deoxyguanosine monophosphate and establish its photodestruction mechanism. 3. Identify the intermediates participating in purine photoinitiated cross linking reactions with organic compounds considered to be models for the side chain of amino acids. The information to be obtained will aid in the understanding of the detrimental effects of UV light on living systems such as mutations, aging and carcinogenesis.

紫外线辐射对 DNA 产生不同类型的损伤 未经修复可能导致致命的、致突变的和致瘤的 影响。 近十年来，已有报道称 紫外线照射的 DNA 中会形成嘌呤光产物， 导致有害影响。 单体的光化学研究 我们实验室的嘌呤及其衍生物表明 光破坏产率与观察到的单体光破坏产率一样高 嘧啶类。 此外，还形成高活性中间体 已被观察到。 这些可能会引发与其他碱基的反应 和/或接近DNA的分子。 我们的主要目标是： 1. 研究和表征激发态和反应态 参与光破坏的中间体 嘌呤脱氧核苷酸二聚体、寡聚体和寡聚体的光化学反应 多核苷酸。 这些将通过它们的吸收来表征 用激光和传统方法获得的光谱和动力学行为 闪光光解和荧光光谱测定。 这些研究将 提供有关最近形成机制的信息 在DNA中观察到嘌呤光产物。 2. 确定光破坏中的稳定产物 脱氧鸟苷和脱氧鸟苷单磷酸并建立其 光破坏机制。 3. 鉴定参与嘌呤的中间体 与有机化合物的光引发交联反应 被认为是氨基酸侧链的模型。 所获得的信息将有助于理解 紫外线对生命系统的有害影响，例如 突变、衰老和致癌。