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

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Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 330)

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 
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Notes

Acknowledgements

This research has been supported by grants from the National Institutes of Health (CA153821 [LHH] and 1S10 RR16659 and CA122952 [DY]) and the National Foundation for Cancer Research (VONHOFF0601 [LHH]). We are grateful to Dr. David Bishop for preparation, proofreading, and editing of the final version of the manuscript.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.College of PharmacyUniversity of ArizonaTucsonUSA
  2. 2.Arizona Cancer CenterTucsonUSA
  3. 3.BIO5 InstituteTucsonUSA

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