Oxidative damage generated by an oxo-metalloporphyrin onto the human telomeric sequence

The cationic metalloporphyrin Mn-TMPyP activated by KHSO5 has been used as cleaver of an oligonucleotide containing the four human telomere repeats of 5'-GGGTTA. This oligonucleotide formed an intramolecular quadruplex DNA un der 200 mM KCl as probed by DMS footprinting and could fold into different quadruplex structures under 200 mM NaCl. We found that the oxo-metalloporph yrin was able to mediate efficient oxidative cleavage of the quadruplex. Th e location of damage showed that the metalloporphyrin was able to bind to t he last G-tetrad of the quadruplex structure via an external interaction. T his metalloporphyrin-G-tetrad interaction needs a relatively high flexibili ty of the single-stranded linker regions to allow the partial stacking of t he metalloporphyrin with the last G-tetrad planar structure. The oxidative damage consisted of guanine oxidation within the interacting G-tetrad toget her with an 1'-carbon hydroxylation of deoxyribose residues of the thymidin e residues located on the neighboring single-stranded loop. So the high-val ent oxo-metalloporphyrin is able to mediate both electron-abstraction or H- abstraction on G or T residues, respectively, within the DNA quadruplex tar get.