Gaining insights into the small molecule targeting of the G-QUADRUPLEX in the c-MYC promoter using NMR and an allele-specific transcriptional assay

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations

Abstract

G-quadruplexes (four-stranded DNA secondary structures) are showing promise as new targets for anticancer therapies. Specifically, G-quadruplexes in the proximal promoter region of regulatory genes have the potential to act as silencer elements and thereby turn off transcription. Thus, compounds that are capable of binding to and stabilizing G-quadruplexes would be of great benefit. In this chapter we describe two recent studies from our labs. In the first case, we use NMR to elucidate the structure of a 2:1 complex between a small molecule and the G-quadruplex in the c-MYC promoter. In the second case, we use an allele-specific transcription assay to demonstrate that the effect of a G-quadruplex-interactive compound is mediated directly through the G-quadruplex. Finally, we use this information to propose models for the interaction of various small molecules with the c-MYC G-quadruplex.

Original languageEnglish (US)
Title of host publicationQuadruplex Nucleic Acids
EditorsJonathan B. Chaires, David Graves
Pages1-22
Number of pages22
DOIs
StatePublished - Apr 11 2013

Publication series

NameTopics in Current Chemistry
Volume330
ISSN (Print)0340-1022

Keywords

  • G-quadruplex
  • NMR structure
  • c-MYC
  • gene regulation

ASJC Scopus subject areas

  • Chemistry(all)

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