Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure

Evonne M. Rezler, Jeyaprakashnarayanan Seenisamy, Sridevi Bashyam, Mu Yong Kim, Elizabeth White, W. David Wilson, Laurence H. Hurley

Research output: Contribution to journalArticle

294 Scopus citations

Abstract

The human telomeric sequence d[T2AG3]4 has been demonstrated to form different types of G-quadruplex structures, depending upon the incubation conditions. For example, in sodium (Na+), a basket-type G-quadruplex structure is formed. In this investigation, using circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-quadruplex-binding ligands affects the conformation of the telomeric G-quadruplex found in solution. The results show that while telomestatin binds preferentially to the basket-type G-quadruplex structure with a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28-diselena sapphyrin chloride (Se2SAP) binds to a different form with a 1:1 stoichiometry in potassium (K+). CD studies suggest that Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce the formation of the basket-type G-quadruplex from a random coil human telomeric oligonucleotide, even in the absence of added monovalent cations such as K+ or Na +. In contrast, in the presence of K+, Se2SAP was found to convert the preformed basket G-quadruplex to the hybrid structure. The significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

Original languageEnglish (US)
Pages (from-to)9439-9447
Number of pages9
JournalJournal of the American Chemical Society
Volume127
Issue number26
DOIs
StatePublished - Jul 6 2005

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure'. Together they form a unique fingerprint.

  • Cite this