Accelerated assembly of G-quadruplex structures by a small molecule

Han Haiyong, Carter L. Cliff, Laurence Hurley

Research output: Contribution to journalArticle

Abstract

In the presence of alkali cations, notably potassium and sodium, DNA oligomers that possess two G-rich repeats associate into either a tetrameric parallel G-quadruplex or a variety of dimeric antiparallel G-quadruplexes. The formation of such structures is normally a very slow process. Some proteins, such as the β-subunit of the Oxytricha telomere-binding protein, promote the formation of G-quadruplex structures in a chaperone-like manner. In this report, we present data concerning the role of a perylene derivative, PIPER, in the assembly of G-quadruplex structures as the first example of a small ligand behaving as a driver in the assembly of polynucleotide secondary structures. Gel-shift experiments demonstrate that PIPER can dramatically accelerate the association of a DNA oligomer containing two tandem repeats of the human telomeric sequence (TTAGGG) into di- and tetrameric G-quadruplexes. In so doing, PIPER alters the oligomer dimerization kinetics from second to first order. The presence of 10 μM PIPER accelerates the assembly of varied dimeric G-quadruplexes an estimated 100-fold from 2 μM oligomer. These results imply that some biological effects elicited by G-quadruplex- interactive agents, such as the induction of anaphase bridges, may stem from the propensity such compounds have for assembling G-quadruplexes.

Original languageEnglish (US)
Pages (from-to)6981-6986
Number of pages6
JournalBiochemistry
Volume38
Issue number22
DOIs
StatePublished - Jun 1 1999
Externally publishedYes

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G-Quadruplexes
Oligomers
Molecules
Telomere-Binding Proteins
Perylene
Polynucleotides
Tandem Repeat Sequences
Dimerization
DNA
Alkalies
Cations
Oxytricha
Potassium
Gels
Sodium
Association reactions
Ligands
Derivatives
Anaphase
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Accelerated assembly of G-quadruplex structures by a small molecule. / Haiyong, Han; Cliff, Carter L.; Hurley, Laurence.

In: Biochemistry, Vol. 38, No. 22, 01.06.1999, p. 6981-6986.

Research output: Contribution to journalArticle

Haiyong, Han ; Cliff, Carter L. ; Hurley, Laurence. / Accelerated assembly of G-quadruplex structures by a small molecule. In: Biochemistry. 1999 ; Vol. 38, No. 22. pp. 6981-6986.
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