Effect of a modified thymine on the structure and stability of [d(TGGGT)]4 quadruplex

Int J Biol Macromol. 2003 Jan 15;31(4-5):131-7. doi: 10.1016/s0141-8130(02)00073-9.

Abstract

Telomeric guanine-rich sequence can adopt quadruplex structures that are important for their biological role in chromosomal stabilisation. G quartets are characterised by the cyclic hydrogen bonding of four guanine bases in a coplanar arrangement and their stability is ion-dependent. In this work we compare the stability of [d(TGGGT)](4) and [d(T*GGGT)](4) quadruplexes. The last one contains a modified thymine, where the hydroxyl group substitutes one hydrogen atom of the methyl group of the thymine in the [d(TGGGT)](4) sequence. We used a combination of spectroscopic, calorimetric and computational techniques to characterise the G-quadruplex formation. NMR and CD spectra of [d(T*GGGT)](4) were characteristic of parallel-stranded, tetramolecular quadruplex. CD and DSC melting experiments reveal that [d(T*GGGT)](4) is less stable that unmodified quadruplex. Molecular models suggest possible explanation for the observed behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Circular Dichroism
  • DNA / chemistry*
  • Guanine / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleic Acid Conformation
  • Temperature
  • Thymine / chemistry*
  • Time Factors

Substances

  • Guanine
  • DNA
  • Thymine