OPTICAL PROPERTIES OF NUCLEIC ACID CONSTITUENTS

核酸成分的光学性质

• 批准号: 3295107
• 负责人: LEIGH B CLARK
• 金额: $ 19.41万
• 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/3295107
• 关键词: DNA binding protein; 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.

拟议的工作旨在发展和完善用于 从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 来理解核酸的动力学和生物学机制。 最强大和广泛使用的光学方法，用于感测详细的 溶液态构象是圆二色性和线性二色性 然而，光谱学两者都需要关于以下的特定光学信息： 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 现在已经可以使用了，因此破坏了的不确定性 在解释寡核的光学性质的信心， 潮汐和核酸正在消失。的主要目标 建议的研究是细化单体数据，探索影响 其他基团存在于这样的系统（核糖，磷酸盐），并研究 这些系统中各种分子间相互作用的影响 （H-键合，堆叠）。因此，建议获得吸收曲线 对于沿着偏振的辐射， 多个单晶体的不同轴。吸收曲线将 从实验偏振反射光谱获得， Kramers-Kronig分析激子耦合将用一个迭代的 程序，努力解释分子间的相互作用， 从晶体光谱中提取自由分子的性质。序列 包括碱基、核苷、核苷酸和离子形式的晶体（如 将进行研究，以回答长期存在的问题， 核糖和磷酸取代和质子化对 碱性发色团氢键A：T和G：C复合物将被检查， 验证和研究从以前唯一的惊人的结论 研究这样的复杂。我们计划培养并检测磷酸二核苷 单晶，以研究堆叠相互作用的影响， 以改进用于计算光学性质的协议， 一般来说，多核苷酸。较长寡核苷酸和药物的晶体 还将寻求研究约束系统。如果时间允许，我们将开始 以检查酰胺和肽基团，以便在结晶时制备 寡核苷酸/多肽复合物的样品变得可用。 最后，我们希望收集一些简单的过渡时刻数据， 分子。这些数据将作为制定 应用于核酸碱基的MO理论方法。