{"doi":"10.1038/s41557-024-01552-7","title":"A folding motif formed with an expanded genetic alphabet","abstract":"Abstract Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ − :dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ − :dZ pairs join parallel strands in a four-stranded compact down–up–down–up fold. These have two possible structures: one with intercalated dZ − :dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC + -reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.","journal":"Nature Chemistry","year":2024,"id":435378,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":272888,"name":"James R. Rocca","orcid":null,"position":1,"is_corresponding":false},{"id":345744,"name":"Shuichi Hoshika","orcid":"0000-0001-9128-1183","position":2,"is_corresponding":false},{"id":1185933,"name":"Cen Chen","orcid":"0000-0002-6883-9369","position":3,"is_corresponding":false},{"id":371833,"name":"Zunyi Yang","orcid":"0000-0002-6245-2040","position":4,"is_corresponding":false},{"id":1203910,"name":"Reza Esmaeeli","orcid":"0000-0001-8679-4267","position":5,"is_corresponding":false},{"id":602160,"name":"Jianguo Wang","orcid":"0000-0003-0984-9716","position":6,"is_corresponding":false},{"id":268375,"name":"Xiaoshu Pan","orcid":"0000-0003-1896-2198","position":7,"is_corresponding":false},{"id":98168,"name":"Jianrong Lu","orcid":"0000-0002-4969-6040","position":8,"is_corresponding":false},{"id":4449,"name":"Kevin Wang","orcid":"0000-0002-9343-6473","position":9,"is_corresponding":false},{"id":1242533,"name":"Y. Charles Cao","orcid":"0000-0001-5476-221X","position":10,"is_corresponding":false},{"id":88885,"name":"Weihong Tan","orcid":"0000-0002-8066-1524","position":11,"is_corresponding":false},{"id":345745,"name":"Steven A. Benner","orcid":"0000-0002-3318-9917","position":12,"is_corresponding":false},{"id":1242532,"name":"Bang Wang","orcid":"0000-0002-5591-2280","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:00:03.406367Z","pmid":"38858518","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":[]}