PREPARATION OF HYBRID DNA CLEAVER OLIGONUCLEOTIDE MOLECULES BASED ON A METALLOTRIS(METHYLPYRIDINIUMYL)PORPHYRIN MOTIF

Methods are reported for conjugating a cationic tris(methylpyridiniumy l)porphyrin-manganese(III) complex to oligonucleotides. The DNA cleave r motif used in the present work is related to Mn-TMPyP, a highly effi cient artificial endonuclease able to hydroxylate C-H bonds of DNA sug ars at nanomolar concentrations. A general coupling method has been de veloped by using porphyrin precursors having a linker attached at the para position of the meso phenyl group of the macrocycle and terminati ng with an activated ester of 1-hydroxybenzotriazole. Coupling reactio ns were monitored by HPLC. Purification of metalloporphyrin-oligonucle otide conjugates was performed by HPLC and desalting on Bio-Gel P-2. T he purity of conjugates was always above 95%.