Hydration is a major determinant of the G-quadruplex stability and conformation of the human telomere 3′ sequence of d(AG 3(TTAG3)3)

M. Clarke Miller, Robert Buscaglia, Jonathan B. Chaires, Andrew N. Lane, John O. Trent

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

The factors that determine the conformation and stability of G-quadruplex forming sequences remain poorly understood. Here we demonstrate the influence of cosolvents on the conformation and stability of the human telomeric sequence d(A(GGGTTA)3GGG)) in both K+ and Na+ containing solutions using a combination of circular dichroism, NMR, and thermodynamics. Molecular crowding arguments have previously been used to suggest that the parallel quadruplex form may be biologically relevant. However, the small cosolvents previously used, PEG 200 and 400, are actually dehydrating agents. We have used acetonitrile as a non-hydrogen-bonding dehydrating agent; similar conformational transitions were observed in K+ solution. Moreover, NMR analysis shows that the resulting structure contains non-anti guanine glycosyl torsion angles suggesting that the conformation present in acetonitrile is not identical to the all-parallel crystal structure, despite the supposed parallel type CD spectrum.

Original languageEnglish (US)
Pages (from-to)17105-17107
Number of pages3
JournalJournal of the American Chemical Society
Volume132
Issue number48
DOIs
StatePublished - Dec 8 2010
Externally publishedYes

ASJC Scopus subject areas

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

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