The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K(+) Solution

Chem Biol Drug Des. 2016 Jul;88(1):122-8. doi: 10.1111/cbdd.12740. Epub 2016 Mar 9.

Abstract

In 80-90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K(+) solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K(+) is extremely controversial, this study provides information for the understanding of different G-quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K(+) solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design.

Keywords: Circular Dichroism; G-quadruplex; anticancer drug; differential scanning calorimetry; telomerase; telomeric DNA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Calorimetry, Differential Scanning
  • Circular Dichroism
  • Drug Design
  • G-Quadruplexes*
  • Humans
  • Models, Molecular*
  • Molecular Weight
  • Native Polyacrylamide Gel Electrophoresis
  • Polydeoxyribonucleotides / chemistry
  • Polydeoxyribonucleotides / metabolism
  • Potassium / chemistry
  • Sodium / chemistry
  • Solubility
  • Telomerase / chemistry
  • Telomerase / metabolism
  • Telomere Shortening*

Substances

  • Antineoplastic Agents
  • Polydeoxyribonucleotides
  • Sodium
  • Telomerase
  • Potassium