Department of Chemistry
Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking
The natural product-like carbamide (1) has been identified as a stabilizer of the c-myc G-quadruplex through high-throughput virtual screening. NMR and molecular modeling experiments revealed a groove-binding mode for 1. The biological activity of 1 against the c-myc G-quadruplex was confirmed by its ability to inhibit Taq polymerase-mediated DNA extension and c-myc expression in vitro, demonstrating that 1 is able to control c-myc gene expression at the transcriptional level presumably through the stabilization of the c-myc promoter G-quadruplex. Furthermore, the interaction between carbamide analogues and the c-myc G-quadruplex was also investigated by in vitro experiments in order to generate a brief structure-activity relationship (SAR) for the observed potency of carbamide 1. © 2012 Ma et al.
Source Publication Title
Public Library of Science
Ma, Dik-Lung, Daniel Shiu-Hin Chan, Wai-Chung Fu, Hong-Zhang He, Hui Yang, Siu-Cheong Yan, and Chung-Hang Leung. "Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking." PLoS ONE 7.8 (2012).