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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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Quadruplex Nucleic Acids

Part of the book series: Topics in Current Chemistry ((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.

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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.

Author information

Authors and Affiliations

  1. College of Pharmacy, University of Arizona, 1703 E. Mabel Street, Tucson, AZ, 85721, USA

    Christine E. Kaiser, Vijay Gokhale, Danzhou Yang & Laurence H. Hurley

  2. Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ, 85724, USA

    Vijay Gokhale, Danzhou Yang & Laurence H. Hurley

  3. BIO5 Institute, 1657 E. Helen Street, Tucson, AZ, 85721, USA

    Vijay Gokhale, Danzhou Yang & Laurence H. Hurley

Authors
  1. Christine E. Kaiser
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  2. Vijay Gokhale
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  3. Danzhou Yang
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  4. Laurence H. Hurley
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Corresponding authors

Correspondence to Danzhou Yang or Laurence H. Hurley .

Editor information

Editors and Affiliations

  1. James Graham Brown Cancer Center, University of Louisville, Louisville, 40202, New York, USA

    Jonathan B. Chaires

  2. , Department of Chemistry, University of Alamaba at Birmingham, 3rd Ave 1530, Birmingham, 35294-1240, Alaska, USA

    David Graves

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© 2012 Springer-Verlag Berlin Heidelberg

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Kaiser, C.E., Gokhale, V., Yang, D., Hurley, L.H. (2012). Gaining Insights into the Small Molecule Targeting of the G-Quadruplex in the c-MYC Promoter Using NMR and an Allele-Specific Transcriptional Assay. In: Chaires, J., Graves, D. (eds) Quadruplex Nucleic Acids. Topics in Current Chemistry, vol 330. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_333

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