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

A new general method for an easy 2'-O-modification of nucleosides is report ed. We describe the preparation of modified 19-mer oligonucleotides carryin g an aminoalkyl linker at the 2'-position of cytidine residues and the cova lent attachment of an artificial chemical nuclease, a manganese(III) tris(N -methylpyridinium-4-yl)porphyrin moiety, onto the functionalized linker. Th e 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 reg ion formed by the 19-mer oligonucleotide vector and a single-stranded DNA t arget. 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.