biostudies-literatureChavan TSNCI NIH HHS7103-19https://www.ebi.ac.uk/biostudies/studies/S-EPMC6270119biostudies-literatureUnknown18(6)NMR is commonly used to investigate macromolecular interactions. However, sensitivity problems hamper its use for studying such interactions at low physiologically relevant concentrations. At high concentrations, proteins or peptides tend to aggregate. In order to overcome this problem, we make use of reductive ¹³C-methylation to study protein interactions at low micromolar concentrations. Methyl groups in dimethyl lysines are degenerate with one ¹³CH₃ signal arising from two carbons and six protons, as compared to one carbon and three protons in aliphatic amino acids. The improved sensitivity allows us to study protein-protein or protein-peptide interactions at very low micromolar concentrations. We demonstrate the utility of this method by studying the interaction between the post-translMolecules (Basel, Switzerland)Application of reductive ¹³C-methylation of lysines to enhance the sensitivity of conventional NMR methods.PMC6270119R01 CA135341Abraham SGaponenko VChavan TSfalseApplication of reductive ¹³C-methylation of lysines to enhance the sensitivity of conventional NMR methods.NMR is commonly used to investigate macromolecular interactions. However, sensitivity problems hamper its use for studying such interactions at low physiologically relevant concentrations. At high concentrations, proteins or peptides tend to aggregate. In order to overcome this problem, we make use of reductive ¹³C-methylation to study protein interactions at low micromolar concentrations. Methyl groups in dimethyl lysines are degenerate with one ¹³CH₃ signal arising from two carbons and six protons, as compared to one carbon and three protons in aliphatic amino acids. The improved sensitivity allows us to study protein-protein or protein-peptide interactions at very low micromolar concentrations. We demonstrate the utility of this method by studying the interaction between the post-transl2013-01-01T00:00:00Z2013 Jun2026-05-06T05:53:52.17Z2025-05-18T13:32:22.369ZS-EPMC62701192377812010.3390/molecules18067103