Accelerated assembly of G-quadruplex structures by a small molecule

Biochemistry. 1999 Jun 1;38(22):6981-6. doi: 10.1021/bi9905922.

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 beta-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 microM PIPER accelerates the assembly of varied dimeric G-quadruplexes an estimated 100-fold from 2 microM 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anthracenes / chemistry
  • Cations, Monovalent
  • DNA / chemistry*
  • DNA Footprinting
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • G-Quadruplexes
  • Guanine / chemistry*
  • Humans
  • Macromolecular Substances
  • Nucleic Acid Conformation*
  • Perylene / analogs & derivatives
  • Piperidines / chemistry
  • Potassium / chemistry
  • Sulfuric Acid Esters / chemistry
  • Tandem Repeat Sequences
  • Telomere / genetics

Substances

  • Anthracenes
  • Cations, Monovalent
  • DNA-Binding Proteins
  • Macromolecular Substances
  • N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide
  • Piperidines
  • Sulfuric Acid Esters
  • Perylene
  • Guanine
  • DNA
  • dimethyl sulfate
  • Potassium