Identification of a selective G-quadruplex DNA binder using a multistep virtual screening approach.
To efficiently identify small molecules binding to a G-quadruplex structure while avoiding binding to duplex DNA, we performed a multistep structure-based virtual screening by simultaneously taking into account G-quadruplex DNA and duplex DNA. Among the 13 compounds selected, one outstanding ligand shows significant selectivity for G-quadruplex binding as determined using SPR, FRET-based competition and luciferase activity assay.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. tanjiah@mail.sysu.edu.cn ceshzs@mail.sysu.edu.cn.
Jin-Qiang
JQ
Hou
Shuo-Bin
SB
Chen
Li-Peng
LP
Zan
Tian-Miao
TM
Ou
Jia-Heng
JH
Tan
Leonard G
LG
Luyt
Zhi-Shu
ZS
Huang
D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance
D008024:Ligands; D016271:Proto-Oncogene Proteins c-myc; D054852:Small Molecule Libraries; D004247:DNA