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DNA序列。 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，我们改进了合成我们需要的构建模块，以制造与炭疽DNA结合的选择性PNA，我们已经开发并发布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细菌中分离的真实的DNA来证实我们的方法可以与真实的系统一起工作。 此外，我们已经将我们的方法与荧光基团结合起来，以创建仅在靶DNA存在下才会发出荧光的发光探针。 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。 在过去的一年里，我们开始与NCI和FDA的研究人员合作，研究使用SV40递送系统将PNA递送到细胞。

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.