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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目包括两个项目：项目1。PNA溶液结构。该提案的目的是表征溶液中PNA/PNA和DNA/DNA双螺旋的结构和动力学，具有不同的金属取代。所获得的结构将被用作输入半经验和从头电子转移（ET）的研究，以研究的顺序，结构，灵活性，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）双链体的分子系统，该系统允许精确控制电子流。该项目是与合成含金属PNA的卡塔利纳·阿奇姆教授、进行电子转移实验的大卫·沃尔德克教授和埃里克·博尔盖教授以及将使用从头算和半经验方法计算电子转移速率的大卫·贝拉坦教授的富有成效的合作。项目2.突变体RT-NNRTI复合物。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，对野生型和突变型RT更有效。我们最近完成了一项研究，研究了几种药物（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（详见进展报告）。为了对这些药物提出修改，我们需要确保我们的结论在突变RT的存在下也是有效的。因此，所提出的修改应该对野生型和常见突变都有效。拟议的研究的目的是了解与突变体RT Lys 103 Asn的相互作用。拟议的药物衍生物将在我们的合作者Brin教授的实验室合成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.