Chemically Modified Peptide Nucleic Acids

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，并激发新型小分子酶抑制剂。 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。 从这些试剂中检测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，我们发现我们的分子非常擅长选择性识别HIV RNA。我们最近发表了第一个X-射线晶体结构，我们修改的PNA绑定到DNA。我们继续改进我们的检测方法，使用我们的PNA分子检测艾滋病患者血浆中的少量HIV。SARS-CoV-2也是一种RNA病毒，我们正在制造新的PNA探针来测试与靶序列的结合。 我们还扩展了一项研究，探索侧链修饰的PNA作为小分子酶抑制剂设计和开发平台的潜力，我们正试图将我们的分子整合到医学诊断的技术平台中。

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 inspire new types of small molecule inhibitors for enzymes. 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 recently published the first X-ray crystallographic structure of our modified PNA bound to DNA. We have continued to refine our assay using our PNA molecules to detect a small amount of HIV in plasma derived from AIDS patients. SARS-CoV-2 is also an RNA virus, and we are making new PNA probes to test for binding to target sequences. We also extended a study exploring the potential of sidechain-modified PNAs as a platform for the design and development of small molecule enzyme inhibitors, and we are trying to integrate our molecules into technological platforms for medical diagnostics.