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Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking.

ABSTRACT: 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.

SUBMITTER: Ma DL

PROVIDER: S-EPMC3422278 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking.

Ma Dik-Lung DL Chan Daniel Shiu-Hin DS Fu Wai-Chung WC He Hong-Zhang HZ Yang Hui H Yan Siu-Cheong SC Leung Chung-Hang CH

PloS one 20120817 8

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 ...[more]

PMID: 22912844

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