Chemically Modified Peptide Nucleic Acids

化学修饰肽核酸

• 批准号: 8939544
• 负责人: DANIEL H APPELLA
• 金额: $ 117.36万
• 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/8939544
• 关键词: Adenosine A2A Receptor; Affinity; Anthrax disease; Base Sequence; Binding; Biological; Biological Assay; Biomedical Research; Bioterrorism; Cellular Membrane; Chemicals; Coupled; Coupling; DNA; DNA Sequence; Detection; Devices; Diagnostic; Disease; G-Protein-Coupled Receptors; Goals; HIV; Ligands; Malignant Neoplasms; Methods; Modification; Monitor; Nanotechnology; Neoplasm Metastasis; Nucleic Acid Binding; Nucleic acid sequencing; Parkinson Disease; Peptide Nucleic Acids; Plasma; Property; RNA; RNA Sequences; Regulation; Research; Single Nucleotide Polymorphism; Specificity; System; Techniques; Technology; Tuberculosis; base; design; improved; interest; nanomaterials; nanopattern; nucleic acid detection; pathogen; receptor; scaffold; self assembly; small molecule; 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 nucleic acids and also to create new type of nano materials for biomedical research. Unique nucleic acid sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of nucleic acids from these agents can be employed as a method to detect their presence or absence, as well as to monitor progression of a specific disease. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA or RNA sequences. We can design our molecules to bind to any sequence of DNA or RNA, 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 continued to refine our assay using our PNA molecules to detect a small amount of HIV in plasma. We also completed a study exploring the potential of sidechain-modified PNAs as basic scaffolds for nanotechnology. Using a system of long DNA sequences, we developed conditions for the self-assembly of specific PNAs onto DNA strands as a way to create nanopatterns of specific biological ligands. We have completed an extensive study using this system to examine the multivalent effects of the adenosine A2A receptor in cellular membranes (which is a G-protein coupled receptor associated with Parkinson's disease).

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核酸序列，并为生物医学研究创造新型纳米材料。 独特的核酸序列与疾病、病原体和许多与生物恐怖主义有关的因子有关。 检测这些病原体的核酸可用作检测其存在或不存在以及监测特定疾病进展的方法。 我们的研究涉及一类与特定DNA或RNA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或RNA序列，以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。 在过去的一年中，我们继续改进我们的检测方法，使用我们的PNA分子检测血浆中的少量HIV。 我们还完成了一项研究，探索侧链修饰的PNA作为纳米技术基本支架的潜力。 使用长DNA序列系统，我们开发了特定PNA自组装到DNA链上的条件，作为创建特定生物配体的纳米粒子的一种方式。 我们已经完成了一项广泛的研究，使用该系统来检查细胞膜中腺苷A2A受体（这是一种与帕金森病相关的G蛋白偶联受体）的多价效应。