Transverse relaxation optimized HCN experiment for nucleic acids: Combining the advantages of TROSY and MQ spin evolution

A three-dimensional MQ-TROSY-HCN pulse sequence is presented which provides intra-base and sugar-to-base correlations for C-13, N-15 labeled nucleic acids (RNA, DNA). The experiment simultaneously exploits the favorable relaxation properties of H-1-C-13 multiple quantum coherence for sugar carbons and of C-13 TROSY-type spin evolution for base carbons. MQ-TROSY-HCN thus combines the advantages of MQ-HCN for sugar-to-base and TROSY-HCN for intra-base correlations in a single experiment. In addition, two slightly different implementations of the MQ-TROSY-HCN experiment ensure optimal performance for small and larger oligonucleotides, respectively. The advantages of the MQ-TROSY-HCN experiment compared to the best previous implementations of HCN are demonstrated for a 33 nucleotide RNA aptamer.