Development and Application of Oligonucleotide Synthesis Methods

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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.