{"doi":"10.1002/anie.202316273","title":"Enhanced TROSY Effect in [2‐<sup>19</sup>F, 2‐<sup>13</sup>C] Adenosine and ATP Analogs Facilitates NMR Spectroscopy of Very Large Biological RNAs in Solution","abstract":"Abstract Large RNAs are central to cellular functions, but characterizing such RNAs remains challenging by solution NMR. We present two labeling technologies based on [2‐ 19 F, 2‐ 13 C]‐adenosine, which allow the incorporation of aromatic 19 F‐ 13 C spin pairs. The labels when coupled with the transverse relaxation optimized spectroscopy (TROSY) enable us to probe RNAs comprising up to 124 nucleotides. With our new [2‐ 19 F, 2‐ 13 C]‐adenosine‐phosphoramidite, all resonances of the human hepatitis B virus epsilon RNA could be readily assigned. With [2‐ 19 F, 2‐ 13 C]‐adenosine triphosphate, the 124 nt pre‐miR‐17‐NPSL1‐RNA was produced via in vitro transcription and the TROSY spectrum of this 40 kDa [2‐ 19 F, 2‐ 13 C]‐A‐labeled RNA featured sharper resonances than the [2‐ 1 H, 2‐ 13 C]‐A sample. The mutual cancelation of the chemical‐shift‐anisotropy and the dipole‐dipole‐components of TROSY‐resonances leads to narrow linewidths over a wide range of molecular weights. With the synthesis of a non‐hydrolysable [2‐ 19 F, 2‐ 13 C]‐adenosine‐triphosphate, we facilitate the probing of co‐factor binding in kinase complexes and NMR‐based inhibitor binding studies in such systems. Our labels allow a straightforward assignment for larger RNAs via a divide‐and‐conquer/mutational approach. The new [2‐ 19 F, 2‐ 13 C]‐adenosine precursors are a valuable addition to the RNA NMR toolbox and will allow the study of large RNAs/RNA protein complexes in vitro and in cells.","journal":"Angewandte Chemie International Edition","year":2024,"id":426776,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1051387,"name":"David Glänzer","orcid":null,"position":1,"is_corresponding":false},{"id":1226248,"name":"Raphael Plangger","orcid":"0009-0007-6279-5629","position":2,"is_corresponding":false},{"id":1010756,"name":"Valentina Kugler","orcid":"0009-0001-1238-9530","position":3,"is_corresponding":false},{"id":1226814,"name":"Jakob Fleischmann","orcid":null,"position":4,"is_corresponding":false},{"id":634366,"name":"Eduard Stefan","orcid":"0000-0003-3650-4713","position":5,"is_corresponding":false},{"id":39808,"name":"David A. Case","orcid":"0000-0003-2314-2346","position":6,"is_corresponding":false},{"id":1226249,"name":"Helena Kovacs","orcid":"0000-0002-5246-9439","position":7,"is_corresponding":false},{"id":465062,"name":"T. Kwaku Dayie","orcid":"0000-0002-7119-4362","position":8,"is_corresponding":false},{"id":274675,"name":"Christoph Kreutz","orcid":"0000-0002-7018-9326","position":9,"is_corresponding":false},{"id":1226813,"name":"Fabian Juen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:58:42.796720Z","pmid":"38185473","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}