Parallel-Stranded Guanine Quadruplex Interactions with a Copper Cationic Porphyrin

Abstract

G-quadruplexes are formed by association of DNA strands containing multiple contiguous guanines. The capability of drugs to induce formation of or stabilize G-quadruplexes is an active area of investigation. We report the interactions of CuTMpyP4, the Cu(2+) derivative of 5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine, with the parallel-stranded G-quadruplexes formed by d(T(4)G(4)T(4)) (1) and d(T(4)G(8)T(4)) (3). Absorption titrations of CuTMpyP4 with (1)(4) or (3)(4) cause both bathochromicity and hypochromicity of the porphyrin Soret band, with larger changes observed for the longer oligonucleotide. An approximate binding constant for (1)(4) and CuTMpyP4 according to the Scatchard model is 5.6 x 10(6) M(-)(1) in terms of quadruplexes and according to the McGhee-von Hippel model is 1.3 x 10(6) M(-)(1) in terms of potential binding sites. An approximate binding constant for (3)(4) and CuTMpyP4 according to the Scatchard model is 5.2 x 10(7) M(-)(1) in terms of quadruplexes and in terms of the McGhee-von Hippel model is 2.4 x 10(6) M(-)(1) in terms of potential binding sites. The site size for CuTMpyP4 and (1)(4) is four using the McGhee-von Hippel model. We find a 2:1 binding stoichiometry for CuTMpyP4 and (1)(4) and a 3:1 binding stoichiometry for CuTMpyP4 and (3)(4) using the method of continuous variation analysis. Induced emission spectra of CuTMpyP4 with (1)(4) or (3)(4) indicate a mode of binding in which the ligand is protected from the solvent. Electron paramagnetic resonance spectra of CuTMpyP4 with added oligonucleotide show an increase in the Cu-N superhyperfine coupling constant as the length of the oligonucleotide increases. On the basis of these data, we propose that for both (1)(4) and (3)(4), CuTMpyP4 molecules externally stack at each end of the run of guanines, similar to other planar G-quadruplex ligands. For (3)(4), our data are consistent with intercalation of a CuTMpyP4 molecule into the G-quadruplex.

Cationic Metal–Corrole Complexes: Design, Synthesis, and Properties of Guanine‐Quadruplex Stabilizers

“…We found that the absorbance was red shifted by less than 8 nm and that the hypochromicity was between 10 and 35 % for the interaction between the corroles and G4 DNA (Table 4). It is suggested that corroles 8, 9, and 12-15 have different binding modes compared with 3 and 4, [33] because of the increased bulkiness of the G4 DNA relative to corroles.…”

The interactions of phenanthroline compounds with DNAs: Preferential binding to telomeric quadruplex over duplex

“…K b is the ratio of slope to the intercept. H% was calculated according to the following formula: [27]. The standard enthalpy change ( H • ), standard entropy change ( S • ) and standard free energy change ( G • ) of compounds 1-3 binding to DNAs were determined by van't Hoff's equation [28]:…”

“…The percent hypochromisms (H%) of the maximum absorption band at 277 nm for the compounds 1-3 were all measured to be about 70%, and their bathochromism values ( ) were about 7 nm. While the significant hypochromism is in the range of intercalation binding, the observed bathochromism values are lower than that of typical intercalation interaction (≥15 nm) [27]. The intrinsic binding constants (K b ) for compounds 1-3 were all calculated in the order of 10 4 M −1 using Eq.…”

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

“…Their affinity is similar or even better than that of non-metalated porphyrin due to a lower electron density on the metalated porphyrin framework allowing higher stacking interaction with G-quartet. In contrast, octahedral complexes with two axial ligands on the metal that would pose a block to stacking interactions, exhibit lower affinity [71,103,112,[121][122][123][124][125]. Logically, due to their strong affinity for DNA duplex, none of these metalated TMPyP4 porphyrins are selective for G4 with respect to double-stranded DNA.…”