{"doi":"10.1073/pnas.2012935118","title":"The 3- <i>O</i> -sulfation of heparan sulfate modulates protein binding and lyase degradation","abstract":"-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":152239,"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":76,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":646525,"name":"Apoorva Joshi","orcid":"0000-0002-8308-5008","position":1,"is_corresponding":false},{"id":646526,"name":"Jiandong Wu","orcid":"0000-0002-4818-4609","position":2,"is_corresponding":false},{"id":646527,"name":"Weigang Lü","orcid":"0000-0002-9016-2729","position":3,"is_corresponding":false},{"id":412283,"name":"Tejabhiram Yadavalli","orcid":"0000-0001-8584-2685","position":4,"is_corresponding":false},{"id":550755,"name":"Margreet A. Wolfert","orcid":"0000-0003-4864-0026","position":5,"is_corresponding":false},{"id":286249,"name":"Deepak Shukla","orcid":"0000-0002-3039-6953","position":6,"is_corresponding":false},{"id":247316,"name":"Joseph Zaia","orcid":"0000-0001-9497-8701","position":7,"is_corresponding":false},{"id":53134,"name":"Geert‐Jan Boons","orcid":"0000-0003-3111-5954","position":8,"is_corresponding":false},{"id":313958,"name":"Pradeep Chopra","orcid":"0000-0002-6003-4574","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:43:22.562252Z","pmid":"33441484","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":[]}