A dumbbell double nicked duplex dodecamer DNA with a PEG6 tether

Org Biomol Chem. 2011 Jun 21;9(12):4481-6. doi: 10.1039/c1ob05103b. Epub 2011 May 17.

Abstract

A hairpin dodecamer DNA motif with a dangling end composed of four bases was studied in order to find conditions which promote a dumbbell structure as the sole form in solution. It could be used as a model of a DNA duplex with two nicks on opposite strands, mimicking a target for topo II poisons. We have established two alternative means of obtaining a dumbbell in solution as the only form present at 0 °C. The first one is to use a relatively high concentration of a hairpin motif, ca. 3.5 mM, at low ionic strength, and second is to use a moderate hairpin motif concentration of ca. 2 mM at high ionic strength, 200 mM and 15% of methanol. An NMR-derived structure in a buffered water solution is presented. A representative structure ensemble of 10 structures was obtained from MD calculations utilizing the AMBER protocol and using NOESY-derived experiment cross peak volumes transferred to experimental restraints by the MARDIGRAS algorithm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA / metabolism
  • DNA Breaks, Single-Stranded
  • DNA Topoisomerases, Type II / chemistry
  • DNA Topoisomerases, Type II / metabolism
  • Humans
  • Inverted Repeat Sequences*
  • Magnetic Resonance Spectroscopy
  • Molecular Dynamics Simulation
  • Molecular Mimicry
  • Nucleic Acid Conformation
  • Polyethylene Glycols / chemistry*
  • Protons
  • Solutions
  • Thermodynamics
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / metabolism

Substances

  • Protons
  • Solutions
  • Topoisomerase II Inhibitors
  • Polyethylene Glycols
  • DNA
  • DNA Topoisomerases, Type II