{"doi":"10.1002/ange.202504640","title":"Antiparallel <i>β</i> ‐Sheet as a Key Motif of Amyloid‐ <i>β</i> Inhibitor Designed via Topological Peptide Reprogramming","abstract":"Abstract Peptide inhibitor design targeting self‐assembly of amyloid‐ β (A β ) represents a promising strategy for suppressing the pathogenic mechanism of Alzheimer's disease (AD). Conventional approaches have primarily mimicked repetitive sequences found in fibrillar structures of A β aggregates. However, since the inherent flexibility of A β structures promotes the structural changes in the early‐stage oligomerization, a structural modulation should be considered in the design of peptide inhibitors. Herein, we introduce topological reprogramming of peptides to control the structural transformation in pathogenic A β 1–42 (A β 42). The eleven‐residue peptide scaffold P a11 ( 14 HQKLVNFAEDV 24 ) identified through the initial screening was dimerized via a disulfide bond. The dimerization stabilizes A β 42 into higher order structures by promoting antiparallel β ‐sheet conformations, thereby significantly suppressing A β 42 aggregation. Our approach underscores that modification in peptide connectivity would be a breakthrough for controlling the intrinsic flexibility of A β , surpassing the limitation in conventional, one‐dimensional peptide building block.","journal":"Angewandte Chemie","year":2025,"id":565637,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1469267,"name":"Ye Eun Lee","orcid":"0000-0001-7151-1009","position":1,"is_corresponding":false},{"id":1469572,"name":"Gyusub Yoon","orcid":null,"position":2,"is_corresponding":false},{"id":80276,"name":"William A. Goddard","orcid":"0000-0003-0097-5716","position":3,"is_corresponding":false},{"id":970935,"name":"Tae Su Choi","orcid":"0000-0002-1515-3275","position":4,"is_corresponding":false},{"id":1469268,"name":"Hugh I. Kim","orcid":"0000-0001-9205-1806","position":5,"is_corresponding":false},{"id":1107812,"name":"Dongjoon Im","orcid":"0000-0002-6206-657X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":null,"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":[]}