Chapter

Quadruplex Nucleic Acids

Volume 330 of the series Topics in Current Chemistry pp 1-21

Date:

Gaining Insights into the Small Molecule Targeting of the G-Quadruplex in the c-MYC Promoter Using NMR and an Allele-Specific Transcriptional Assay

  • Christine E. KaiserAffiliated withCollege of Pharmacy, University of Arizona
  • , Vijay GokhaleAffiliated withCollege of Pharmacy, University of ArizonaArizona Cancer CenterBIO5 Institute
  • , Danzhou YangAffiliated withCollege of Pharmacy, University of ArizonaArizona Cancer CenterBIO5 Institute Email author 
  • , Laurence H. HurleyAffiliated withCollege of Pharmacy, University of ArizonaArizona Cancer CenterBIO5 Institute Email author 

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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.

Keywords

G-quadruplex c-MYC gene regulation NMR structure