{"doi":"10.1073/pnas.76.3.1218","title":"Correlation between structure and function of heparin","abstract":"<jats:p>\n                    We have fractionated crude porcine heparin to obtain highly active as well as relatively inactive species of molecular weight ≈7000 with specific anticoagulant activities of 360 and 12 units/mg, respectively. Nitrous acid degradation of both of these polymers yielded a tetrasaccharide fraction, 1β, that contained equimolar amounts of iduronic and glucuronic acids, possessed an internal\n                    <jats:italic>N</jats:italic>\n                    -acetylated glucosamine, and carried anhydromannitol at the reducing end position. The 1β tetrasaccharide derived from the highly active heparin, 1β\n                    <jats:italic>a</jats:italic>\n                    , was recovered in a yield of 1.1 mol/7000 daltons. Our analyses indicate that at least 95% of the 1β\n                    <jats:italic>a</jats:italic>\n                    is a single structure that consists of the following unique monosaccharide sequence: L-iduronic acid →\n                    <jats:italic>N</jats:italic>\n                    -acetylated D-glucosamine-6-sulfate → D-glucuronic acid →\n                    <jats:italic>N</jats:italic>\n                    -sulfate D-glucosamine-6-sulfate. The 1β tetrasaccharide fraction from relatively inactive mucopolysaccharide, 1β\n                    <jats:italic>i</jats:italic>\n                    , was recovered in a yield of 0.3 mol/7000 daltons and was a mixture of several components. Only 8.5% of the 1β\n                    <jats:italic>i</jats:italic>\n                    tetrasaccharide fraction exhibited the same uronic acid placement and sulfate group position found in 1β\n                    <jats:italic>a</jats:italic>\n                    . Thus, 2.6% of relatively inactive mucopolysaccharide molecules contain the unique tetrasaccharide sequence found within each molecule of highly active heparin. Given the correlation between abundance of this unique 1β\n                    <jats:italic>a</jats:italic>\n                    tetrasaccharide sequence and biologic potency, we suggest that this structure represents the critical site responsible for anticoagulant activity.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1979,"id":639774,"datarank":14.736211440775811,"base_score":5.648974238161206,"endowment":5.648974238161206,"self_citation_contribution":0.847346135724181,"citation_network_contribution":13.888865305051631,"self_endowment_contribution":0.847346135724181,"citer_contribution":13.888865305051631,"corpus_percentile":null,"corpus_rank":null,"citation_count":283,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1662455,"name":"Lun Lam","orcid":null,"position":1,"is_corresponding":false},{"id":1662454,"name":"Robert D. Rosenberg","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Correlation between structure and function of heparin","abstract":"<jats:p>\n                    We have fractionated crude porcine heparin to obtain highly active as well as relatively inactive species of molecular weight ≈7000 with specific anticoagulant activities of 360 and 12 units/mg, respectively. Nitrous acid degradation of both of these polymers yielded a tetrasaccharide fraction, 1β, that contained equimolar amounts of iduronic and glucuronic acids, possessed an internal\n                    <jats:italic>N</jats:italic>\n                    -acetylated glucosamine, and carried anhydromannitol at the reducing end position. The 1β tetrasaccharide derived from the highly active heparin, 1β\n                    <jats:italic>a</jats:italic>\n                    , was recovered in a yield of 1.1 mol/7000 daltons. Our analyses indicate that at least 95% of the 1β\n                    <jats:italic>a</jats:italic>\n                    is a single structure that consists of the following unique monosaccharide sequence: L-iduronic acid →\n                    <jats:italic>N</jats:italic>\n                    -acetylated D-glucosamine-6-sulfate → D-glucuronic acid →\n                    <jats:italic>N</jats:italic>\n                    -sulfate D-glucosamine-6-sulfate. The 1β tetrasaccharide fraction from relatively inactive mucopolysaccharide, 1β\n                    <jats:italic>i</jats:italic>\n                    , was recovered in a yield of 0.3 mol/7000 daltons and was a mixture of several components. Only 8.5% of the 1β\n                    <jats:italic>i</jats:italic>\n                    tetrasaccharide fraction exhibited the same uronic acid placement and sulfate group position found in 1β\n                    <jats:italic>a</jats:italic>\n                    . Thus, 2.6% of relatively inactive mucopolysaccharide molecules contain the unique tetrasaccharide sequence found within each molecule of highly active heparin. Given the correlation between abundance of this unique 1β\n                    <jats:italic>a</jats:italic>\n                    tetrasaccharide sequence and biologic potency, we suggest that this structure represents the critical site responsible for anticoagulant activity.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.648974238161206,"endowment":5.648974238161206,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"286307","pmcid":"PMC383221","openalex_id":"https://openalex.org/W2040042544","authors":[],"funders":[],"total_grants":0,"fwci":7.2093,"citation_percentile":0.97663829,"influential_citations":0,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":4},{"year":2014,"count":2},{"year":2015,"count":5},{"year":2016,"count":8},{"year":2017,"count":4},{"year":2018,"count":8},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":5},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/383221","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/383221","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.76.3.1218","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.76.3.1218","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/286307","host_type":"repository"}],"fields_of_study":["Proteoglycans and glycosaminoglycans research","Glycosylation and Glycoproteins Research","Protease and Inhibitor Mechanisms","Animals","Carbohydrates","Glucuronates","Heparin","Molecular Weight","Oligosaccharides","Structure-Activity Relationship","Sulfuric Acids","Swine"],"mesh_terms":["Animals","Carbohydrates","Glucuronates","Heparin","Molecular Weight","Oligosaccharides","Structure-Activity Relationship","Sulfuric Acids","Swine"],"keywords":["Tetrasaccharide","Chemistry","Iduronic acid","Glucuronic acid","Glucosamine","Uronic acid","Stereochemistry","Sulfate","Yield (engineering)","Monosaccharide","Biochemistry","Organic chemistry","Polysaccharide"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T01:34:10.533049Z","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":[]}