Formation of a Complex of 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin with G-Quadruplex DNA

Abstract

A water-soluble cationic porphyrin, 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TmPyP4), has been studied extensively because of its unique physicochemical properties that lead to interactions with nucleic acids, as well as its therapeutic application. Formation of a complex between TmPyP4 and parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), has been characterized in an effort to elucidate the mode of molecular recognition between TmPyP4 and the DNA. The study demonstrated that TmPyP4 intercalates into the A3pG4 step of [d(TTAGGG)]4 with an association constant of 6.2 x 10(6) M(-1) and a stoichiometric ratio of 1:1. The binding of TmPyP4 to the A3pG4 step of [d(TTAGGG)]4 was found to be stabilized by the pi-pi stacking interaction of the porphyrin ring of TmPyP4 with the G4 quartet as well as the A3 bases of the G-quadruplex DNA. These findings provide novel insights for the design of porphyrin derivatives that bind to DNA with high affinity and specificity.

Studies on synthesis, characterization, and G-quadruplex binding of Ru(II) complexes containing two dppz ligands

“…Therefore, many research groups have designed and synthesized some molecules with such structures, which are believed to be able to interact with G-quadruplex DNA structures. This interaction plays an important role to maintain the telomeres [11][12][13][14][15]. Furthermore, inducement/stabilization features of G-quadruplex structures by small molecules directly prevent elongation of telomeres by disrupting the interaction between the enzyme and its substrate.…”

Synthesis, characterization and RNA-binding properties of a novel ruthenium(II) complex coordinated by 5-pyridine-10,15,20-triphenylporphyrin

“…For one thing, ruthenium(II) complexes, which have the mimic structure to cis-platinum, have long been investigated as potent agent in chemotherapy and photodynamic therapy for their high affinity to double strand DNA helix [1][2][3][4][5][6][7][8][9][10][11]. In recent decades, a number of ruthenium(II) complexes have been designed and synthesized, and the DNA-binding properties and antitumor activity of these complexes have been studied extensively.…”

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

“…The second one ( Figure 11B) is a solution NMR structure (with c-myc oncogene promoter DNA sequence), which shows the porphyrin interacting with the top G-quartet, although at a relatively long distance (4.5 Å), not in perfect accordance with known - stacking distances [105]. In addition, a the complex of H 2 -TMPyP4 with the parallel quadruplex formed by the association of four 5'-d(TTAGGG) strands was analyzed by NMR and proposes also that the porphyrin stands in contact with the 5'-side external guanine quartet yet in sandwich between the Gquartet and the first A3 base adjacent to it [106].…”

“…Porphyrin H 2 -TMPyP4 interacts with telomeric G-quadruplex models with a relatively high binding constant, in the order of Ka~10 6 -10 8 M -1 [97,101,[106][107][108]. The binding of H 2 -TMPyP4 to the c-myc promoter parallel quadruplex is tighter with a binding constant of Ka~10 8 -10 9 M -1 [109].…”