Synthesis and DNA cleavage of 2′-O-amino-linked metalloporphyrin–oligonucleotide conjugates

Abstract

A new general method for an easy 2′-O-modification of nucleosides is reported. We describe the preparation of modified 19-mer oligonucleotides carrying an aminoalkyl linker at the 2′-position of cytidine residues and the covalent attachment of an artificial chemical nuclease, a manganese(III) tris(N-methylpyridinium-4-yl)porphyrin moiety, onto the functionalized linker. The positions of attachment of the manganese cationic porphyrin within the 19-mer vector sequence and the length of the tether were selected in order to have the DNA-cleaver entity close to an (AT)₃-sequence in the duplex region formed by the 19-mer oligonucleotide vector and a single-stranded DNA target. The cleavage pattern of the target DNA by these new metalloporphyrin–oligonucleotide conjugates was compared with that obtained with the 19-mer oligonucleotide conjugate carrying the metalloporphyrin at the 5′-end.