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

O. Yu Fedoroff, A. Rangan, V. V. Chemeris, L. H. Hurley

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Telomeric C-rich strands can form a noncanonical intercalated DNA structure known as an i-motif. We have studied the interactions of the cationic porphyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl)porphine (TMPyP4) with the i-motif forms of several oligonucleotides containing telomeric sequences. TMPyP4 was found to promote the formation of the i-motif DNA structure. On the basis of 1H NMR studies, we have created a model of the i-motif-TMPyP4 complex that is consistent with all the available experimental data. Two-dimensional NOESY data prompted us to conclude that TMPyP4 binds specifically to the 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 intriguing possibility that TMPyP4 can trigger the formation of unusual DNA structures in both strands of the telomeres, which may in turn explain the recently documented biological effects of TMPyP4 in cancer cells.

Original languageEnglish (US)
Pages (from-to)15083-15090
Number of pages8
JournalBiochemistry
Volume39
Issue number49
DOIs
StatePublished - Dec 12 2000

ASJC Scopus subject areas

  • Biochemistry

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