Raman study of potential "antisense" drugs: nonamer oligonucleotide duplexes with a central mismatch as a model system for the binding selectivity evaluation

Biopolymers. 2004;74(1-2):115-9. doi: 10.1002/bip.20056.

Abstract

A set of four 9-mer oligonucleotide duplexes formed between the 5'-GCATNTCAC-3', N=A,C,T,G, and the 5'-GTGATATGC-3' complement has been proposed as a model system for the investigation of novel oligonucleotide analogues (candidates for antisense use) binding selectivity. Raman measurements were carried out on a set of natural DNA 9-mer in order to verify suitability of the model and to obtain reference spectral data. Difference Raman spectra between the mismatch and match duplexes obtained at 15 degrees C exhibited numerous spectral features sensitively indicating the structural changes. All the three mismatches only very weakly disturb the overall B-form conformation of the duplex. Significant structural changes that occurred at the mismatch site are reflected mainly by the neighboring thymidine Raman bands at 1377, 1650, and 1675 cm(-1). The intensity change of the two latter bands is almost the same for the T:G and the T:T mismatch while in the case of the T:C mismatch it is just opposite, demonstrating a very different arrangement of the mismatched pair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • DNA / chemistry
  • Magnetic Resonance Spectroscopy
  • Oligonucleotides / chemistry
  • Oligonucleotides, Antisense / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Spectrum Analysis, Raman / methods*
  • Thermodynamics

Substances

  • Oligonucleotides
  • Oligonucleotides, Antisense
  • DNA