{"doi":"10.1002/anie.202314597","title":"Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide‐Activated Sirtuin 7**","abstract":"-dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.","journal":"Angewandte Chemie International Edition","year":2023,"id":340314,"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":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":741995,"name":"Alexander L. Nielsen","orcid":"0000-0003-1195-0143","position":1,"is_corresponding":false},{"id":1074769,"name":"Iben Jensen","orcid":"0009-0008-3598-1757","position":2,"is_corresponding":false},{"id":1074770,"name":"Tobias Hansen","orcid":"0000-0001-6098-058X","position":3,"is_corresponding":false},{"id":1074771,"name":"Line A. Ryberg","orcid":"0000-0002-5301-0232","position":4,"is_corresponding":false},{"id":804862,"name":"Samuel T. Jameson","orcid":null,"position":5,"is_corresponding":false},{"id":1074772,"name":"Pernille Harris","orcid":"0000-0002-6806-4903","position":6,"is_corresponding":false},{"id":361413,"name":"Günther H. Peters","orcid":"0000-0001-9754-2663","position":7,"is_corresponding":false},{"id":281307,"name":"John M. Denu","orcid":"0000-0001-9415-0365","position":8,"is_corresponding":false},{"id":764649,"name":"Joseph M. Rogers","orcid":"0000-0002-1313-4089","position":9,"is_corresponding":false},{"id":90538,"name":"Christian A. Olsen","orcid":"0000-0002-2953-8942","position":10,"is_corresponding":false},{"id":804195,"name":"Julie E. Bolding","orcid":"0000-0003-2735-2519","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T01:10:54.145367Z","pmid":"37873919","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":[]}