Ultraviolet resonance Raman spectroscopy of locked single‐stranded oligo(dA) reveals conformational implications of the locked ribose in LNA

We report here the first UV resonance Raman spectroscopic (UVRRS) study on locked nucleic acid (LNA) oligomers. Locking a base in nucleic acid (NA) oligomers produces a conformational change in the glycosyl bond between backbone and base. We present evidence of this change in LNAs when compared to their natural analogs using UVRRS. Wavenumber downshifts and peak amplitude increases, especially of the ∼1481 cm−1 peak that is a spectral marker for part of the glycosyl bond, correlate with the fraction of locked bases when single‐stranded oligomers incorporating up to three locked bases were examined. By varying the position of the locked base within a fixed length sequence, we conclude that one, or at most two bases, on either side of the lock is affected. We further conclude from these data, and previously published reports, that the conformation of LNA is determined by imidazole–imidazole and pyrimidine–pyrimidine repulsion and imidazole–pyrimidine attraction in contrast to dispersion attraction‐dependent aggregation in the B conformation of DNA.