Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism

Telomeric C-rich strands can form a noncanonical intercalated DNA structure known as an i-motif. We have studied the interactions of the cationic porp hyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl)porphine (TMPyP4) with the i-mot if forms of several oligonucleotides containing telomeric sequences. TMPyP4 was found to promote the formation of the i-motif DNA structure. On the ba sis of H-1 NMR studies, we have created a model of the i-motif-TMPyP4 compl ex that is consistent with all the available experimental data. Two-dimensi onal NOESY data prompted us to conclude that TMPyP4 binds specifically to t he edge of the intercalated DNA core by a nonintercalative mechanism. Since we have shown that TMPyP4 binds to and stabilizes the G-quadruplex form of the complementary G-rich telomeric strand, this study raises the intriguin g possibility that TMPyP4 can trigger the formation of unusual DNA structur es in both strands of the telomeres, which may in turn explain the recently documented biological effects of TMPyP4 in cancer cells.