G-quadruplexes as targets for drug design

Laurence H. Hurley, Richard T. Wheelhouse, Daekyu Sun, Sean M. Kerwin, Miguel Salazar, Oleg Yu Fedoroff, Frank X. Han, Haiyong Han, Elzbieta Izbicka, Daniel D. Von Hoff

Research output: Contribution to journalArticle

210 Scopus citations

Abstract

G-quadruplexes are a family of secondary DNA structures formed in the presence of monovalent cations that consist of four-stranded structures in which Hoogsteen base-pairing stabilizes G-tetrad structures. These structures are proposed to exist in vivo, although direct confirmatory evidence is lacking. Guanine-rich regions of DNA capable of forming G-quadruplex structures are found in a variety of chromosomal regions, including telomeres and promoter regions of DNA. In this review, we describe the design of three separate groups of G-quadruplex-interactive compounds and their interaction with G-quadruplex DNA. Using the first group of compounds (anthraquinones), we describe experiments that provide the proof of concept that a G-quadruplex is required for inhibition of telomerase. Using the second group of compounds (perylenes), we describe the structure of a G-quadruplex-ligand complex and its effect on the dynamics of formation and enzymatic unwinding of the quadruplex. For the third group of compounds (porphyrins), we describe the experiments that relate the biological effects to their interactions with G-quadruplexes. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)141-158
Number of pages18
JournalPharmacology and Therapeutics
Volume85
Issue number3
DOIs
StatePublished - Mar 1 2000
Externally publishedYes

Keywords

  • Anthraquinone
  • G-quadruplex
  • Perylene
  • Porphyrin
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'G-quadruplexes as targets for drug design'. Together they form a unique fingerprint.

  • Cite this

    Hurley, L. H., Wheelhouse, R. T., Sun, D., Kerwin, S. M., Salazar, M., Fedoroff, O. Y., Han, F. X., Han, H., Izbicka, E., & Von Hoff, D. D. (2000). G-quadruplexes as targets for drug design. Pharmacology and Therapeutics, 85(3), 141-158. https://doi.org/10.1016/S0163-7258(99)00068-6