Direct Measurement of Sequential Folding Pathway and Energy Landscape of Human Telomeric G-quadruplex Structures

J Am Chem Soc. 2013 May 1;135(17):6423-6. doi: 10.1021/ja4019176. Epub 2013 Apr 23.


Single-stranded guanine-rich sequences fold into compact G-quadruplexes. Although G-triplexes have been proposed and demonstrated as intermediates in the folding of G-quadruplexes, there is still a debate on their folding pathways. In this work, we employed magnetic tweezers to investigate the folding kinetics of single human telomeric G-quadruplexes in 100 mM Na(+) buffer. The results are consistent with a model in which the G-triplex is an in-pathway intermediate in the folding of the G-quadruplex. By finely tuning the force exerted on the G-quadruplex, we observed reversible transitions from the G-quadruplex to the G-triplex as well as from the G-triplex to the unfolded coil when the force was increased from 26 to 39 pN. The energy landscape derived from the probability distribution shows clearly that the G-quadruplex goes through an intermediate when it is unfolded, and vice versa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Buffers
  • Circular Dichroism
  • DNA / chemistry
  • Electromagnetic Fields
  • Energy Transfer
  • G-Quadruplexes*
  • Guanine / chemistry*
  • Humans
  • Kinetics
  • Nucleic Acid Conformation
  • Telomere / chemistry*
  • Thermodynamics


  • Buffers
  • Guanine
  • DNA