X RAY STUDIES OF NUCLEIC ACID CONSTITUENTS

核酸成分的 X 射线研究

• 批准号: 6018288
• 负责人: MUTTAIYA SUNDARALINGAM
• 金额: $ 22.61万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6018288
• 关键词: DNA; RNA; X ray crystallography; chemical binding; conformation; ligands; model design /development; netropsin; nucleic acid chemical synthesis; nucleic acid structure; oligonucleotides; physical model

DESCRIPTION: Structural studies on nucleic acids are essential to understand the genetics of living organisms. This proposal will continue the crystal structural work on A-form oligonucleotides and drug complexes of B-DNA and RNA. The work will provide the limits of nucleic acid conformation, details of the tertiary structures of the duplexes, novel base-pairing schemes, base triples and quartets and multiple modes of drug interactions. Since A-DNA packs with the termini abutting into the body of neighboring duplexes, different from the packing of other nucleic acids, other packing modes will be sought. Alternating sequences with a 5'-purine start generally form A-DNA, but the all-GC decamer d(GCGCGCGCGC) sequence forms a left-handed Z-DNA. While the decamer d(GCACGCGTCG) with all four bases, AT interposing the GC's, is A-DNA. This case will be investigated with a single A*T base pair substituting for a G*C base pair at different positions in a 10-mer and a 12-mer. Drug complexes of different B-DNA sequences will be studied to see whether they form side-by-side or end-to-end complexes or other binding modes. Hybrid DNA-RNA structures will be investigated to determine if the sugar puckering modes are like B-DNA (C2'-endo) or RNA (C3'-endo) or a mixture. The O2'-hydroxyl group, which makes RNA different from DNA, will be studied for its role in intra and inter-duplex hydrogen bonding and formation of tertiary structures. Long (16-mers and longer) RNA oligonucleotides, both with and without mispairs and bulges, will be investigated. The crystal structures will be compared with the solution structures to gain further insight into the differences between the solid state and the solution state. The oligonucleotides will be synthesized and crystallized and the intensity data collected on an in-house R-Axis IIc Imaging plate/Siemens area detector systems. The structures will be solved by molecular replacement or by the heavy atom method and refined by XPLOR. The structural work will be invaluable to better understand health, gene regulation and rational drug design.

描述：核酸的结构研究对于 了解生物的遗传学。 该建议将继续 A形式寡核苷酸和药物复合物的晶体结构工作 B-DNA和RNA。 该工作将提供核酸的限制 构象，双链体第三级结构的细节，新颖 碱基配对方案，基本三元组和四重奏以及多种药物模式 互动。 由于A-DNA与末端的包装包装到了身体 相邻的双链体，不同于其他核酸的包装， 将寻求其他包装模式。 与5-钢铁交替序列 启动通常形成A-DNA，但全GC Decamer D（GCGCGCGCGC）序列 形成左手z-DNA。 而decamer d（gcacgcgtcg）均具有四个 基地在插入GC时是A-DNA。 此案将进行调查 用单个A*t碱基对在不同的 位于10分钟和12分钟的位置。 不同B-DNA的药物复合物 将研究序列以查看它们是并排形成还是 端到端复合物或其他绑定模式。 混合DNA-RNA结构将 进行研究以确定糖泡制模式是否像B-DNA （C2'-endo）或RNA（C3'-endo）或混合物。 O2'-羟基，该组 使RNA与DNA不同，将研究其在内部和 双链氢键和三级结构的形成。 长的 （16-mers及更长的）RNA寡核苷酸，无论有无过程 和凸起，将进行调查。 将比较晶体结构 使用解决方案结构以进一步了解差异 在固态和溶液状态之间。 寡核苷酸将 合成并结晶，并收集的强度数据 内部R轴IIC成像板/西门子区域检测器系统。 这 结构将通过分子置换或重原子来解决 方法并通过Xplor精制。 结构性工作对于 更好地了解健康，基因调节和合理的药物设计。