Two main problems are found in NMR studies of nucleic acids: Extensive resonance overlapping and conformationally-dependent NOE-based assignment strategy that can be partially overcomed using labeled compounds. The basic NMR experiments and strategy for unlabeled nucleic acids are summarized:

• Through-bond assignments
• Sugar ¹H and ¹³C resonances
• Sequential sugar ¹H via the intervening ³¹P.
• Non-exchangeable base protons.
• Intranucleotide sugar-to-base correlations.
• Exchangeable imino and amino ¹H and ¹⁵N base resonances.
• Through-space assignments