OPTICAL PROPERTIES OF NUCLEIC ACID CONSTITUENTS

核酸成分的光学性质

• 批准号: 3295112
• 负责人: LEIGH B CLARK
• 金额: $ 15.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295112
• 关键词: DNA binding protein; X ray crystallography; adenine; benzimidazoles; chromophore; circular dichroism; conformation; crystallization; dichroism; dinucleotide; electronic spectra; hydrogen bond; molecular dynamics; molecular stacking; monomer; nucleic acid structure; nucleobase; oligonucleotides; phosphates; polarimetry; polynucleotides; ribose; solutions; spectrometry; thymine; ultraviolet spectrometry

The proposed work is aimed at developing and refining methods used to obtain nucleic acid conformations in solution from optical measurements. Such information and the corresponding models it produces are prerequisite for understanding the dynamics and biological mechanisms of nucleic acids. The most powerful and widely used optical methods for sensing detailed solution state conformations are circular dichroism and linear dichroism spectroscopies, however both require specific optical information regarding the electric dipole transition moments of the purine and pyrimidine monomeric chromophores. Much of the essential monomer information is just now becoming available, so that the uncertainties that have undermined confidence in the interpretation of the optical properties of oligonucleo- tides and nucleic acids are disappearing. The principal aims of the proposed research is to refine the monomer data, to explore the effects of other groups present in such systems (ribose, phosphate) and to investigate the effects of the various intermolecular interactions in such systems (H-bonding, stacking). It is therefore proposed to obtain absorption curves extending well into the vacuum UV region for radiation polarized along various axes of a multitude of single crystals. The absorption curves will be obtained from experimental polarized reflection spectra through Kramers-Kronig analysis. Exciton coupling will be treated with an iterative procedure in an effort to account for intermolecular interactions and to extract free molecule properties from the crystal spectra. Sequences of crystals including base, nucleoside, nucleotide and ionic forms (as available) will be studied in order to answer long-standing questions about the effects of ribose and phosphate substitution and protonation on the base chromophore. Hydrogen bonded A:T and G:C complexes will be examined to verify and study the striking conclusions drawn from the only previous study of such a complex. We plan to grow and examine dinucleoside phosphate single crystals in order to study the effects of stacking interactions and to refine the protocols for calculating the optical properties of polynucleotides in general. Crystals of longer oligonucleotides and drug bound systems will also be sought for study. As time permits we will begin to examine the amide and peptide groups so as to be prepared when crystal specimens of oligonucleotide/polypeptide complexes become available. Finally, we hope to collect transition moment data on a few simpler molecules. Such data will serve as a guide in the development of MO-theoretical methods as applied to the nucleic acid bases.

拟议的工作旨在开发和改进用于 通过光学测量获得溶液中的核酸构象。 这些信息及其产生的相应模型是先决条件 以了解核酸的动力学和生物机制。 最强大和最广泛使用的光学方法来检测详细信息 溶液状态构象有圆二色和线性二向色性 然而，分光镜和分光镜都需要关于 嘌呤和嘧啶的电偶极跃迁矩 单体发色团。许多基本的单体信息只是 现在变得可用了，所以破坏了 对解释寡核光学性质的置信度- 潮汐和核酸正在消失。该计划的主要目标 提出的研究是为了提炼单体数据，探索影响 这类系统中存在的其他基团(核糖、磷酸)并研究 这类体系中各种分子间相互作用的影响 (氢键、堆叠)。因此，建议获得吸收曲线 很好地延伸到真空紫外区，辐射沿 许多单晶的不同轴。吸收曲线将 由实验偏振反射光谱通过 Kramers-Kronig分析。激子耦合将用迭代方法来处理 在努力解释分子间相互作用和 从晶体光谱中提取自由分子的性质。序列 晶体包括碱基、核苷、核苷酸和离子形式(AS )将被研究，以回答长期存在的关于 核糖和磷酸取代及质子化对核糖和磷酸的影响 碱性发色团。氢键A：T和G：C络合物将被检查以 验证和研究从之前唯一的 对这种情结的研究。我们计划培养和检测二核苷磷酸 单晶，以研究堆积相互作用的影响和 改进用于计算光学性质的协议 一般是多核苷酸。较长的寡核苷酸晶体和药物 受约束的系统也将被寻找进行研究。只要时间允许，我们将开始 检查氨基和多肽基团，以便在结晶时制备 可以获得寡核苷酸/多肽复合体的样本。 最后，我们希望收集几个更简单的过渡时刻数据 分子。这些数据将作为制定 适用于核酸碱基的分子轨道理论方法。