{"doi":"10.1021/jacs.1c04378","title":"Stapled β-Hairpins Featuring 4-Mercaptoproline","abstract":"Peptides constrained by intramolecular cross-links, especially stapled α-helices, have emerged as versatile scaffolds for drug development. However, there are fewer examples of similarly constrained scaffolds for other secondary structures. Here, we used a novel computational strategy to identify an optimal staple for antiparallel β-strands, and then we incorporated that staple within a β-hairpin peptide. The hairpin uses 4-mercaptoproline as a novel staple component, which contributes to a unique, kinked structure. The stapled hairpins show a high degree of structure in aqueous solution, excellent resistance to degradation in cell lysates, and cytosolic penetration at micromolar concentrations. They also overlay with a unique subset of kinked hairpin motifs at protein-protein interaction interfaces. Thus, these scaffolds represent promising starting points for developing inhibitors of cellular protein-protein interactions.","journal":"Journal of the American Chemical Society","year":2021,"id":172839,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":709304,"name":"Bryan J. Lampkin","orcid":"0000-0002-8633-1227","position":1,"is_corresponding":false},{"id":709702,"name":"Charles Abakah","orcid":null,"position":2,"is_corresponding":false},{"id":249508,"name":"Adam Moyer","orcid":"0000-0001-9245-4541","position":3,"is_corresponding":false},{"id":9651,"name":"J. Miao","orcid":"0000-0003-1112-1927","position":4,"is_corresponding":false},{"id":313068,"name":"Kirsten Deprey","orcid":null,"position":5,"is_corresponding":false},{"id":398014,"name":"Robert A. Cerulli","orcid":"0000-0002-6043-4789","position":6,"is_corresponding":false},{"id":651034,"name":"Yu‐Shan Lin","orcid":"0000-0001-6460-2877","position":7,"is_corresponding":false},{"id":420698,"name":"James Baleja","orcid":"0000-0003-4841-0247","position":8,"is_corresponding":false},{"id":105706,"name":"David Baker","orcid":"0000-0001-7896-6217","position":9,"is_corresponding":false},{"id":311642,"name":"Joshua A. Kritzer","orcid":"0000-0003-2878-6781","position":10,"is_corresponding":false},{"id":263205,"name":"Jennifer R. Pace","orcid":"0000-0003-2275-1991","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:46:41.424716Z","pmid":"34516087","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":[]}