Chemically Modified Peptide Nucleic Acids

化学修饰肽核酸

• 批准号: 7593519
• 负责人: daniel appella
• 金额: $ 43.94万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593519
• 关键词: Affinity; Anthrax disease; Bacteria; Binding; Biological; Biological Assay; Bioterrorism; Cells; Chemicals; Class; Collaborations; Color; Condition; Coupled; Coupling; DNA; DNA Sequence; Detection; Development; Diagnostic; Disease; Genes; Goals; HIV; Malignant Neoplasms; Methods; Modification; Nucleic Acid Binding; Peptide Nucleic Acids; Production; Property; Publishing; RNA Sequences; Research; Research Personnel; Simian virus 40; Single Nucleotide Polymorphism; Specificity; System; Technology; United States Food and Drug Administration; Work; antigene; base; design; improved; interest; pathogen; tool

Our research on Peptide Nucleic Acids (abbreviated as PNAs) focuses on introducing chemical modifications that will make this class of molecules broadly useful to detect sequences of DNA. Unique DNA sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of DNA from these agents can be employed as a method to detect their presence or absence. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA sequences. We can design our molecules to bind to any sequence of DNA, and previously we have found that our molecules are extremely good at selective recognition of DNA associated with anthrax. During the past year, we have imporved the synthesis of the building blocks we need to make selective PNAs that bind to anthrax DNA, and we have developed, and published, a color-based detection assay using our PNA molecules to detect anthrax DNA. We have also used real DNA isolated from the anthrax bacteria to comfirm that our methods can work with a real system. In addition, we have coupled our methods with fluorescent groups to create light-up probes that will only fluoresce in the presence of target DNA. PNAs are also useful as antisense and antigene molecules, however delivery into cells has been difficult. This past year we have begun a collaboration with researchers in the NCI and FDA examining the delivery of PNA to cells using an SV40 delivery system.

我们对多肽核酸(缩写为PNAS)的研究集中在引入化学修饰，使这类分子在检测DNA序列方面具有广泛的用途。独特的DNA序列与疾病、病原体和许多与生物恐怖主义有关的病原体有关。从这些试剂中检测DNA可以用作检测它们的存在或不存在的方法。我们的研究涉及合成一类与特定DNA序列结合的非天然分子(称为PNA)。我们可以设计我们的分子与任何DNA序列结合，之前我们发现我们的分子在选择性识别与炭疽相关的DNA方面非常好。在过去的一年里，我们改进了构建块的合成，我们需要制造与炭疽DNA结合的选择性PNA，我们已经开发并发表了一种基于颜色的检测方法，使用我们的PNA分子来检测炭疽DNA。我们还使用了从炭疽菌中分离出来的真实DNA，以确保我们的方法可以在真实的系统中工作。此外，我们还将我们的方法与荧光基团结合起来，创建了只有在目标DNA存在的情况下才会发光的发光探针。PNA作为反义和抗基因分子也很有用，但很难进入细胞。在过去的一年里，我们开始与NCI和FDA的研究人员合作，检查使用SV40递送系统将PNA递送到细胞的情况。