Synthesis of orthogonally protected peptide nucleic acid (PNA) building block for attachment of groups to C5 of U

ORGN 142

Ajay Kshetry, akkshetr@artsci.wustl.edu and John S. Taylor. Department of Chemistry, Washington University in St. Louis, One Brookings Drive, Forsyth Blvd, Saint Louis, MO 63141

Because of its biological stability, hybridization and duplex invading properties, peptide nucleic acid (PNA) has been used for the construction of a variety of bioconjugates with novel biological and biotechnological applications.  Many bioconjugates of PNA have been made by conjugating molecules to the ends of PNA, but there are a number of applications that could benefit from the attachment to internal positions of the PNA.  We will describe a facile synthesis of an orthogonally protected PNA building block for solid phase Fmoc synthesis that can be used to attach groups to the C5 of U via an amino group.  The building block can be conveniently prepared from hydroxymethyl uracil in 6 steps.  We will also report on the synthesis of other derivatives of U.