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Natural Abundance
Biomolecular NMR with 13C and 15N at natural abundance
Isotope labelling of protein, DNA and RNA samples is usually necessary for heteronuclear NMR. The reason for this is either the low sample concentration entailing low sensitivity or the intrinsically low sensitivity of some of the experiments which rely on magnetisation transfer over the 13C and 15N heteronuclei. The high sensitivity of cryogenically cooled probes, however, allows for experiments that formerly required full isotope labelling, on biomolecules containing one heteronucleus either at natural abundance or partially labelled.
Advantages:
- Working at natural abundance will reduce the overall cost as isotope-labelling may be expensive.
- Initial investigations can be undertaken with a singly 15N labelled protein.
- Isotope-labelling of DNA and RNA fragments can be avoided, though this is often difficult as it is done through synthesis. Natural abundance of 13C is preferred.

- 3D HNCA spectrum recorded with 13C at natural abundance. The sample was 2mM 15N-labelled ubiquitin in 50mM phosphate buffer at pH 5.8. The data were collected on a 800 MHz triple resonance CryoProbe, total experiment time being 5 hours.
