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Raman study of potential "antisense" drugs: nonamer oligonucleotide duplexes with a central mismatch as a model system for the binding selectivity evaluation
Authors:Nemecek Daniel  Stepanek Josef  Turpin Pierre-Yves  Rosenberg Ivan
Affiliation: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
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.
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