Chemically Modified Peptide Nucleic Acids

我们对多肽核酸(PNAS)的研究集中在引入化学修饰，使这类分子在检测DNA序列和抑制特定疾病的进展方面具有广泛的用途。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病原体有关。从这些试剂中检测DNA可以用作检测它们的存在或不存在的方法。我们的研究涉及合成一类与特定DNA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任何DNA序列结合，之前我们发现我们的分子在选择性识别与炭疽相关的DNA方面非常好。在过去的一年里，我们继续改进我们的检测方法，使用我们的PNA分子来检测低至60个副本的炭疽DNA，并探索了检测的定量和定性区域。我们还将这一策略扩展到检测HIV RNA。PNA作为反义和抗基因分子也很有用，但很难进入细胞。我们有了一个新的合作，基于已知的细菌蛋白质寻找特定的递送试剂，帮助将货物运输到细胞内。最后，我们还完成了一项研究，探索其他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，作为一种创建特定生物配体的纳米颗粒的方法，并将其应用于提高小环肽(CRGD)在小鼠模型中抑制癌症转移的效率。我们现在正在将这个系统扩展到生物学中的其他多价领域。

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 continued to refine our assay using our PNA molecules to detect as few as 60 copies of anthrax DNA and we explored the quantitative and qualitative regions of detection. We have also extended this strategy to detect HIV RNA. PNAs are also useful as antisense and antigene molecules, however delivery into cells has been difficult. We have a new collaboration looking for specific delivery agents based on known bacterial proteins that help transport cargo into cells. Finally, we also completed a study exploring the potential of other 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 and we have applied this to improve the efficacy of a small cyclic peptide (cRGD) for inhibition of cancer metastasis in a mouse model. We are now extending this system to other areas of multivalency in biology.