Chemically Modified Peptide Nucleic Acids

我们对多肽核酸(PNAS)的研究主要集中在引入化学修饰，使这类分子在检测核酸序列方面具有广泛的用途，并为生物医学研究创造新型的纳米材料。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素有关。从这些病原体中检测核酸可以作为一种方法来检测它们的存在或不存在，以及监测特定疾病的进展。我们的研究涉及合成一类与特定DNA或RNA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DNA或RNA的任何序列结合，我们发现我们的分子在选择性识别HIV RNA方面非常好。我们继续改进我们的检测方法，使用我们的PNA分子来检测血浆中的少量艾滋病毒。我们还扩展了一项研究，探索侧链修饰的PNA作为纳米技术基础支架的潜力。使用长DNA序列系统，我们开发了将特定的PNA自组装到DNA链上的条件，作为创建特定生物配体的纳米分子的一种方式。我们已经使用这个系统完成了一项广泛的研究，以检查细胞膜上的多巴胺D2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。

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 we have found that our molecules are extremely good at selective recognition of HIV RNA. We have continued to refine our assay using our PNA molecules to detect a small amount of HIV in plasma. We also extended 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 dopamine d2 receptor in cellular membranes (which is a G-protein coupled receptor associated with Parkinson's disease).