Chemically Modified Peptide Nucleic Acids

化学修饰肽核酸

• 批准号: 7967326
• 负责人: DANIEL H APPELLA
• 金额: $ 53.78万
• 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/7967326
• 关键词: Affinity; Anthrax disease; Bacterial Proteins; Binding; Biological; Biological Assay; Bioterrorism; Cells; Chemicals; Chemistry; Collaborations; Coupling; DNA; DNA Sequence; Detection; Diagnostic; Disease; Genes; Goals; HIV; Influenza A Virus, H1N1 Subtype; Ligands; Malignant Neoplasms; Methods; Modification; Nanotechnology; Nucleic Acid Binding; Peptide Nucleic Acids; Production; Property; RNA Sequences; Research; Single Nucleotide Polymorphism; Specificity; System; Techniques; Technology; antigene; base; biological systems; design; improved; interest; nanopattern; pathogen; scaffold; self assembly; small molecule; swine flu; tool; tumor progression

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 and to suppress the progression of specific diseases. 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 improved the chemistry to make our molecules, and have continued to refine our assay using our PNA molecules to detect anthrax DNA. We are currently looking to extend our detection system to the H1N1 (swine) flu. PNAs are also useful as antisense and antigene molecules, however delivery into cells has been difficult. We are starting a collaboration looking for specific delivery agents based on known bacterial proteins that help transport cargo into cells. Finally, we are exploring the potential of other PNAs as basic scaffolds for nanotechnology. Using a system of long DNA sequences, we are developing conditions for the self-assembly of specific PNAs onto DNA strands as a way to create nanopatters of specific biological ligands.

我们对肽核酸（缩写为PNA）的研究重点是引入化学修饰，使这类分子广泛用于检测DNA序列和抑制特定疾病的进展。 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物质有关。 从这些试剂中检测DNA可用作检测其存在或不存在的方法。 我们的研究涉及一类与特定DNA序列结合的非天然分子（称为PNA）的合成。 我们可以设计我们的分子来结合任何DNA序列，之前我们已经发现我们的分子非常擅长选择性识别与炭疽有关的DNA。 在过去的一年里，我们改进了化学方法来制造我们的分子，并继续改进我们的检测方法，使用我们的PNA分子来检测炭疽DNA。 我们目前正在寻求将我们的检测系统扩展到H1N1（猪）流感。 PNA也可用作反义和抗基因分子，然而递送到细胞中一直是困难的。 我们正在开始一项合作，寻找基于已知细菌蛋白的特定递送剂，以帮助将货物运输到细胞中。 最后，我们正在探索其他PNA作为纳米技术基本支架的潜力。 使用长DNA序列系统，我们正在开发特定PNA自组装到DNA链上的条件，作为创建特定生物配体纳米图案的一种方式。