Oy. Fedoroff et al., Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism, BIOCHEM, 39(49), 2000, pp. 15083-15090
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.