Development and Application of Oligonucleotide Synthesis Methods

所提出的研究包括合成新型的“正交”固相载体。它们将用于制备受保护的寡核苷酸，以及与固定在指定位置的官能团或肽连接的寡核苷酸结合物。还将制备相关的寡核苷酸。这项研究将扩大可用于将寡核苷酸从固体载体上切割出来的反应类型，包括还原反应和酶反应，并扩大可用于偶联受保护寡核苷酸的化学范围。通过这一续展奖项，有机和高分子化学项目支持科罗拉多州立大学化学系马克·M·格林伯格博士的研究。研究的重点是开发固相载体，在温和的条件下可以从固相载体上切割受保护的DNA和RNA片段，并扩大可用于扩大连接形成低聚物的核苷酸数量的反应谱系。这项工作将为其他试图合成寡核苷酸的人提供有用的方法，并将具有实际的生物医学应用。研究生和博士后研究员将接受小分子和生物聚合物合成方面的培训，并获得不断增长的生物技术领域所需的培训。

The proposed research involves the synthesis of novel `orthogonal` solid phase supports. These will be used for the preparation of protected oligonucleotides, and oligonucleotide conjugates with functional groups or peptides attached at defined positions. Related oligoribonucleotides will also be prepared. The research will extend the types of reactions that can be used to cleave the oligonucleotides from the solid support to include reductive and enzymatic reactions, and extend the scope of chemistry available for conjugating protected oligonucleotides. With this renewal award, the Organic and Macromolecular Chemistry Program supports the research of Dr. Marc M. Greenberg of the Department of Chemistry at Colorado State University. The research focuses on developing solid phase supports from which protected fragments of DNA and RNA can be cleaved under mild conditions, and on expanding the repertoire of reactions available for extending the number of nucleotides linked to form the oligomers. The work will provide useful approaches to others attempting to synthesize oligonucleotides, and will have practical biomedical applications. Graduate students and post-doctoral fellows will receive training in the synthesis of small molecules and biopolymers, and get the kind of training needed in the growing biotechnology area.