A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of C-MYC G-quadruplex and Down-regulates C-MYC Transcription in Human Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2015 Aug 20

PMID 26286633

Citations 12

Authors

Deepanjan Panda

Manish Debnath

Samir Mandal

Irene Bessi

Harald Schwalbe

Jyotirmayee Dash

Affiliations

Soon will be listed here.

Abstract

The c-MYC proto-oncogene is a regulator of fundamental cellular processes such as cell cycle progression and apoptosis. The development of novel c-MYC inhibitors that can act by targeting the c-MYC DNA G-quadruplex at the level of transcription would provide potential insight into structure-based design of small molecules and lead to a promising arena for cancer therapy. Herein we report our finding that two simple bis-triazolylcarbazole derivatives can inhibit c-MYC transcription, possibly by stabilizing the c-MYC G-quadruplex. These compounds are prepared using a facile and modular approach based on Cu(I) catalysed azide and alkyne cycloaddition. A carbazole ligand with carboxamide side chains is found to be microenvironment-sensitive and highly selective for "turn-on" detection of c-MYC quadruplex over duplex DNA. This fluorescent probe is applicable to visualize the cellular nucleus in living cells. Interestingly, the ligand binds to c-MYC in an asymmetric fashion and selects the minor-populated conformer via conformational selection.

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