INCORPORATING NEW BASE PAIRS INTO NUCLEIC ACID ANALOGS

已经开发了一类新的生物聚合物，其结合了联合收割机的分子 具有扩展功能的DNA和RNA的识别特性， 化学多样性如在核酸中，互补的“链”的互补链是互补的。 生物聚合物通过沃森-克里克碱基配对规则识别彼此。 此外，我们已经表明，这些生物聚合物可以复制在一个 使用DNA和RNA的多种模板指导的生物聚合反应 聚合酶子分子本身可以编码子分子， 分子。并且应该可以探索分子多样性， 这些分子通过突变和选择的过程。与DNA不同， 然而，RNA。这些生物聚合物是由12个基本单元组成的， 比只有4。其中几种结构单元带有官能团 其为生物聚合物提供了许多结构通用性， 更复杂的分子，如蛋白质。该项目的目标是 建立使用DNA和RNA聚合酶的可行性，以前 初步鉴定，通过聚合酶链扩增生物聚合物 反应型过程。寻求的商业产品是寡核苷酸 它们是生物受体的配体， 用于诊断测定的配体和可标记的标签 与自然产生的核酸结合 拟议的商业应用： 碱基对和包含它们的寡核苷酸类似物包括 药物发现和诊断。通过创造分子 多样性，具有扩增的化学结构的寡核苷酸类似物的文库 可以产生功能性用于筛选作为针对靶的配体， 受体。在诊断领域，需要分子标签或手柄 其不与天然存在的寡核苷酸交叉反应，但 它可以形成基 与互补的新碱基配对。

A new class of biopolymers has been developed that combine the molecular recognition properties of DNA and RNA with expanded functionality and chemical diversity. As in nucleic acids, complementary' strands of the biopolymer recognize each other by Watson-Crick base pairing rules. Further, we have shown that these biopolymers can be replicated in a variety of template-directed biopolymerization reactions using DNA and RNA polymerases. The daughter molecules can themselves encode daughter, molecules. and it should be possible to explore molecular diversity with these molecules via a process of mutation and selection. Unlike DNA and RNA, however. these biopolymers are built from 12 building blocks rather than only 4. Several of these building blocks carry functional groups which provide the biopolymer with much of tile structural versatility of more complex molecules such as proteins. The goal of this project is to establish the feasibility of using DNA and RNA polymerases, previously identified in preliminary, to amplify the biopolymer by a polymerase chain reaction-type process. The commercial products sought are oligonucleotides that are ligands for biological receptors, receptors for biological ligands and amplifiable tags for diagnostic assays that do not cross react with naturally-occurring nucleic acids. PROPOSED COMMERCIAL APPLICATIONS: The commercial applications for novel base pairs and oligonucleotide analogs in which they are contained include drug discovery and diagnostics. Through the creation of molecular diversity, libraries of oligonucleotide analogs with expanded chemical functionality can be created for screening as ligands against target receptors. In the diagnostic area, molecular tags or handles are desired that do not cross-react with naturally-occurring oligonucleotides, but which can form base pairs with a complementary novel base.