{"doi":"10.1002/anie.202211985","title":"Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library","abstract":"Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number of HS oligosaccharides. To overcome the obstacles and expedite the synthesis, a divergent approach was designed, where 64 HS tetrasaccharides covering all possible structures of 2-O-, 6-O- and N-sulfation with the glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from a single strategically protected tetrasaccharide intermediate. This extensive library helped identify the structural requirements for HS sequences to have strong fibroblast growth factor-2 binding but a weak affinity for platelet factor-4. Such a strategy to separate out these two interactions could lead to new HS-based potential therapeutics without the dangerous adverse effect of heparin-induced thrombocytopenia.","journal":"Angewandte Chemie International Edition","year":2022,"id":249543,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490927,"name":"Sherif Ramadan","orcid":"0000-0002-8639-4105","position":1,"is_corresponding":false},{"id":288983,"name":"Guowei Su","orcid":"0000-0003-2668-9275","position":2,"is_corresponding":false},{"id":890943,"name":"Chang‐Xin Huo","orcid":null,"position":3,"is_corresponding":false},{"id":890254,"name":"Yuetao Zhao","orcid":"0000-0001-5338-0789","position":4,"is_corresponding":false},{"id":288986,"name":"Jian Liu","orcid":"0000-0001-8552-1400","position":5,"is_corresponding":false},{"id":363255,"name":"Linda C. Hsieh‐Wilson","orcid":"0000-0001-5661-1714","position":6,"is_corresponding":false},{"id":308597,"name":"Xuefei Huang","orcid":"0000-0002-6468-5526","position":7,"is_corresponding":false},{"id":890942,"name":"Kedar N. Baryal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:23.754337Z","pmid":"36173931","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":[]}