Improvement of porphyrins for G-quadruplex DNA targeting.
G-quadruplex nucleic acids are emerging as therapeutic targets for small mols. referred to as small-mol. G-quadruplex ligands. The porphyrin H2-TMPyP4 was early reported to be a suitable motif for G-quadruplex DNA recognition. It probably binds to G-quadruplex nucleic acid through $π$-$π$ stacking with the external G-quartets. The authors explored chem. modifications of this porphyrin such as insertion of various metal ions in the center of the arom. core and addn. of bulky substituents that may improve the specificity of the compd. toward G-quadruplex DNA. Porphyrin metalation, affording a G4-ligand with two sym. faces, allowed the conclusion that the presence of an axial water mol. perpendicular to the arom. plane lowered but did not hamper $π$-$π$ stacking interactions between the arom. parts of the ligand on the one hand and the external G-quartet on the other. The charge introduced in the center of the porphyrin had little influence on binding. Thus, the ionic channel in the center of G-quadruplex nucleic acids was not found to provide clear addnl. mol. clues for G-quadruplex nucleic acid targeting by the porphyrins tested. Furthermore, the authors confirmed the unique G-quadruplex selectivity of a porphyrin modified with four bulky substituents at the meso positions and showed that although the compd. is not "drug-like" it was capable of entering cells in culture and mediated some of the typical cellular effects of small-mol. G-quadruplex ligands. [on SciFinder(R)]
Références
- Titre
- Improvement of porphyrins for G-quadruplex DNA targeting.
- Type de publication
- Article de revue
- Année de publication
- 2011
- Auteurs
- Romera, Carmen, Bombarde Oriane, Bonnet Romaric, Gomez Dennis, Dumy Pascal, Calsou Patrick, Gwan Jean-Fang, Lin Jung-Hsin, Defrancq Eric, and Pratviel Genevieve.
- Revue
- Biochimie
- Volume
- 93
- Pagination
- 1310–1317
- ISSN
- 0300-9084
- Mots-clés
- porphyrin binding G quadruplex DNA
Soumis le 12 avril 2018