ROAMING: SOLUTION STRUCTURE OF PNA AND DNA DOUBLE-HELICES WITH AND WITHOUT META

漫游：带或不带 Meta 的 PNA 和 DNA 双螺旋的解结构

• 批准号: 7956221
• 负责人: MARCELA MADRID
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956221
• 关键词: Anti-HIV Agents; Binding; Biomedical Research; Charge; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; Electron Transport; Electronics; Ensure; Funding; Generations; Goals; Grant; HIV-1 Reverse Transcriptase; High Performance Computing; Institution; Laboratories; Metals; Methods; Modification; Molecular; Mutation; Peptide Nucleic Acids; Pharmaceutical Preparations; Progress Reports; RNA-Directed DNA Polymerase; Research; Research Personnel; Resources; Solutions; Solvents; Source; Structure; System; United States National Institutes of Health; base; design; flexibility; mutant; research study

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. This proposal consists of two projects: Project 1. PNA solution structure. The objectives of this proposal are to characterize the structure and dynamics of PNA/PNA and DNA/DNA double helices in solution, with different metal substitutions. The obtained structures will be used as input to semi-empirical and ab initio electron transfer (ET) studies, in order to study the effect of sequence, structure, flexibility, solvent and charge on ET. Our long-term goal is to design and synthesize molecular systems based on metal-peptide nucleic acids (metal-PNA) duplexes, which allow the precise control of electronic flow. This project is a fruitful collaboration with Prof. Catalina Achim, who synthesizes metal-containing PNA, Prof. David Waldeck and Eric Borguet, who conduct electron transfer experiments, and Prof. David Beratan, who will use ab-initio and semi-empirical methods to calculate electron transfer rates. Project 2. Mutant RT-NNRTI complexes. The long term goal of our HIV-1 reverse transcriptase (RT) research is to design new anti-AIDS drugs, more effective against wild-type and mutant RT. We have recently completed a study of the interactions of several drugs (including the latest generation, more effective, DAPYs) in the binding pocket of wild-type RT (as detailed in the Progress Report). In order to propose modifications to these drugs, we need to ensure that our conclusions are also valid in the presence of mutant RT. The proposed modifications should, then, be effective against both wild-type and commonly occurring mutations. The objectives of the proposed research are to understand the interactions with mutant RT Lys103Asn. The proposed drug derivatives will be synthesized in the laboratory of our collaborator, Prof. Brin.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本方案由两个项目组成：项目1.PNA解决方案结构。该方案的目的是表征不同金属取代的PNA/PNA和DNA/DNA双螺旋在溶液中的结构和动力学。所获得的结构将被用作半经验和从头算电子转移(ET)研究的输入，以研究序列、结构、柔性、溶剂和电荷对ET的影响。我们的长期目标是设计和合成基于金属-肽核酸(金属-PNA)双链的分子系统，这使得电子流动能够得到精确的控制。这个项目是与Catalina Achim教授的卓有成效的合作，他合成了含有金属的PNA，David Waldeck教授和Eric Borguet教授进行了电子转移实验，David Beratan教授将使用从头算和半经验方法来计算电子转移速率。项目2.突变的RT-NNRTI复合体。我们HIV-1逆转录酶(RT)研究的长期目标是设计新的抗艾滋病药物，更有效地对抗野生型和突变型RT。我们最近完成了一项关于几种药物(包括最新一代、更有效的DAPY)在野生型RT结合口袋中的相互作用的研究(如进度报告所述)。为了对这些药物提出修改建议，我们需要确保我们的结论在突变RT存在的情况下也是有效的。因此，拟议的修改应该对野生型和常见突变都有效。这项研究的目的是了解突变的RT Lys103Asn之间的相互作用。建议的药物衍生物将在我们的合作者Brin教授的实验室合成。