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

✍ Scribed by Daniel Nemecek; Josef Stepanek; Pierre-Yves Turpin; Ivan Rosenberg

• Publisher: Wiley (John Wiley & Sons)
• Year: 2004
• Tongue: English
• Weight: 134 KB
• Volume: 74
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20056

✦ Synopsis

Abstract

A set of four 9‐mer oligonucleotide duplexes formed between the 5′‐GCAT__N__TCAC‐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°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. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004