Preparation of hybrid "DNA cleaver-oligodeoxyribonulceotide" molecules based on a metallotris (methylpyridiniumyl)porphyrin motif

Abstract

Methods are reported for conjugating a cationic tris(methylpyridiniumyl)porphyrin-manganese(III) complex to oligonucleotides. The DNA cleaver motif used in the present work is related to Mn-TMPyP, a highly efficient artificial endonuclease able to hydroxylate C-H bonds of DNA sugars at nanomolar concentrations. A general coupling method has been developed by using porphyrin precursors having a linker attached at the para position of the meso phenyl group of the macrocycle and terminating with an activated ester of 1-hydroxybenzotriazole. Coupling reactions were monitored by HPLC. Purification of metalloporphyrin-oligonucleotide conjugates was performed by HPLC and desalting on Bio-Gel P-2. The purity of conjugates was always above 95%.