Cobalt(iii)porphyrin to target G-quadruplex DNA

Abstract

G-quadruplex DNA ligands attract much attention because of their potential use in biology. Indeed they may interfere with G-quadrulex nucleic acid function in cells. Most of the G-quadruplex ligands so far reported (including also metal complexes) are large planar aromatic compounds that interact by π-π stacking with an external G-quartet of quadruplex. Porphyrins are well-known G-quadruplex ligands. We report herein a new porphyrin scaffold (meso-tetrakis(4-(N-methyl-pyridinium-2-yl)phenyl)porphyrin) able to strongly and selectively bind to G-quadruplex DNA. We show that even when this porphyrin is metallated with cobalt(III), i.e. it carries two water molecules as axial ligands on the cobalt ion, on each face of the porphyrin, the interaction occurs by a π-stacking-like mode with an external G-quartet of quadruplex DNA.

New Ruthenium‐Based Probes for Selective G‐Quadruplex Targeting

“…The interaction with the G‐quadruplex grooves and loops is also taken into account for improving the selectivity for G‐quadruplex versus duplex DNA. Among the compounds able to target G‐quadruplexes, a number of metal complexes bearing aromatic ligands have been reported, including those of porphyrin, salphens, and salophens . In this context, we have designed a new extended planar ligand, based on a pyrazine core, namely dipyrazino[2,3‐ a :2′,3′‐ h ]phenazine (dph; Figure a).…”

Efficient Inhibition of Telomerase by Nickel–Salophen Complexes

“…[13] The most representative inorganic compounds that interact with G 4 -DNA are metal complexes of porphyrin [14] and salophen [15] ligands,p rovided that they are functionalized by cationic arms. We recently showed that nickel(II)-salophen complexes functionalized at both para positions by alkylmethylimidazolium groups [15e] bind strongly and specifically to G-quadruplexes.…”

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

“…Bulky porphyrin derivatives H 2 -TMPipEOPP, H 2 -TMPy2PP, H 2 -GP, H 2 -DIGPor and H 2 -TPyEtCAP can perfectly discriminate between quadruplex and double-stranded DNA [63,69,71,[116][117][118][119][120]. Their binding constants for quadruplex DNA is comparable to that of best G4 ligands [120].…”

“…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. In the case of bulky cationic porphyrins the influence of the central metal on the binding capacity of the metalated derivatives is less documented [69,71,119,120]. It seems that the presence of axial ligands on the metal does not always lower the binding capacity to quadruplex DNA.…”