Raman study of potential "antisense" drugs: nonamer oligonucleotide duplexes with a central mismatch as a model system for the binding selectivity evaluation.
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.
Nemecek
Daniel
D
Université P. et M. Curie, L.P.B.C., CNRS URA 2056, 4 Place Jussieu, Case 138, F-752 52 Paris Cedex 05, France. nemecek@karlov.mff.cuni.cz
Stepanek
Josef
J
Turpin
Pierre-Yves
PY
Rosenberg
Ivan
I
D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013816:Thermodynamics
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D004247:DNA