Raman Study of Potential 'Antisense' Drugs: Nonamer Oligonucleotide Duplexes with a Central Mismatch as a Model System for the Binding Selectivity Evaluation

Abstract

A set of four 9-mer oligonucleotide duplexes based on 5 -d(GCATNTCAC)-3 oligonucleotide and four its complements with the central base N=A,C,T,G has been proposed as a model system for the investigation binding selectivity of novel oligonucleotide analogues (candidates for antisense use) to fully complementary sequences. Difference Raman spectra between the mismatch and match duplexes obtained at 15°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.