Development and Application of Oligonucleotide Synthesis Methods

提出的研究涉及新型“正交”固相支架的合成。这些将用于制备受保护的寡核苷酸，以及在指定位置连接官能团或肽的寡核苷酸偶联物。相关的寡核苷酸也将被制备。该研究将扩展可用于从固体载体上切割寡核苷酸的反应类型，包括还原和酶促反应，并扩展可用于偶联受保护寡核苷酸的化学范围。有了这个更新奖，有机和大分子化学项目支持科罗拉多州立大学化学系的马克·m·格林伯格博士的研究。该研究的重点是开发在温和条件下可以裂解受保护的DNA和RNA片段的固相载体，以及扩展可用于扩展连接形成低聚物的核苷酸数量的反应库。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。研究生和博士后将接受小分子和生物聚合物合成方面的培训，并获得不断发展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.