Use of competition dialysis in the discovery of G-quadruplex selective ligands.
G-quadrplex DNA can exist in a rich variety of structural forms, ranging from unimolecular folded structures containing diverse types of loops and strand oreintations, to bimolecular dimeric structures, and finally to tetramolecular parallel-stranded structures. These diverse structures present numerous potential small molecule binding sites with distinctive properties. There is mounting evidence for important functional roles for G-quadruplex structures in biology. G-quadruplexes may participate in the maintenance of telomeres, in transcriptional regulation and, in mRNA, may act to modulate translation. G-quadruplexes thus represent an attractive target for new small-molecule therapeutic agents. Competition dialysis provides a useful tool for the discovery of small molecules that selectively recognize the unique structural features of G-quadruplexes. The principles and practice of the competition dialysis experiment are described here.
Ragazzon
Patricia
P
James Graham Brown Cancer Center, University of Louisville, 529 S. Jackson St., Louisville, KY 40202, USA.
Chaires
Jonathan B
JB
D003956:Dialysis; D015195:Drug Design; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008024:Ligands; D013816:Thermodynamics
D008024:Ligands; D006147:Guanine