Building Blocks for Ribozyme Mimics: Conjugates of Terpyridine and Bipyridine with Nucleosides

The incorporation of the 2,2‘:6‘,2‘‘-terpyridyl (terpy) complex of Cu(II) into a deoxyoligonucleotide has led to a functional mimic of ribozymes. The resulting mimic can cleave target RNA in a sequence-directed manner by a hydrolytic mechanism. Here we describe the synthesis and characterization of four modified nucleoside phosphoramidite reagents ( 7, 10, 14, and 18 ) that contain pendant 2,2‘-bipyridine or terpy ligands. The ligands are attached either to the nucleobase ( 7, 10 ) or to the sugar ( 14, 18 ). Nucleobase modification was carried out at the C-5 position of 2‘-deoxyuridine (dU). One route to sugar modification was performed by synthesis of 18, a 1‘-functionalized analog of dU based on 1-[3-deoxy-β- d -psicofuranosyl]uracil. Another route to sugar functionaliztion resulted in 14, a 2‘-O-alkyl derivative of adenosine. These modified nucleosides are building blocks for ribozyme mimics. They are designed to deliver hydrolytically active metal complexes across either the major groove ( 7, 10 ) or the minor groove ( 14, 18 ) of an RNA/DNA duplex.