Quantifying interactions between G-quadruplex DNA and transition-metal complexes.
Telomerase inhibition through guanine quadruplex sequestration by small-molecule drugs is of great current interest as an anticancer strategy. G-quadruplexes (GQs) can be formed at the guanine-rich sequences found at the end of the telomere. They possess a large electron-rich pi-surface which is favorable for the binding of electron-poor small molecules. Small molecules binding to GQs can sequester the telomere ends and inhibit the enzyme telomerase, which is expressed in cancer cells and absent in normal somatic cells. Transition-metal complexes present a myriad of geometries and numerous ligand coordination environments and allow for modular syntheses for development of compound libraries to target GQs. We have demonstrated the size of the pi-surface, binding selectivity and affinity of phenanthroimidazole platinum (II) complexes [PtPIX(en)](2+)2PF (6) (-) (X = naphthyl, phenyl and en = ethylenediamine) and metallosupramolecular complexes [Pt(4,4'-bpy)(en)] (4) (8+) 8PF (6) (-) (where bpy = bipyridine) to GQs can be readily tuned and assayed through a number of biophysical techniques.
Kieltyka
Roxanne
R
Department of Chemistry, McGill University, Montreal, QC, Canada.
Englebienne
Pablo
P
Moitessier
Nicolas
N
Sleiman
Hanadi
H
D002846:Chromatography, Affinity / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D008652:Mesoporphyrins / Q000737:chemistry*; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism*; D012685:Sepharose / Q000737:chemistry
D008652:Mesoporphyrins; D009944:Organoplatinum Compounds; C031468:mesoporphyrin IX; D006147:Guanine; D004247:DNA; D012685:Sepharose