{"doi":"10.1002/chem.202401108","title":"Chemoenzymatic Synthesis of Tri‐antennary <i>N</i>‐Glycans Terminating in Sialyl‐Lewis<sup>x</sup> Reveals the Importance of Glycan Complexity for Influenza A Virus Receptor Binding","abstract":"Abstract Sialyl‐Lewis x (SLe x ) is involved in immune regulation, human fertilization, cancer, and bacterial and viral diseases. The influence of the complex glycan structures, which can present SLe x epitopes, on binding is largely unknown. We report here a chemoenzymatic strategy for the preparation of a panel of twenty‐two isomeric asymmetrical tri‐antennary N ‐glycans presenting SLe x ‐Le x epitopes on either the MGAT4 or MGAT5 arm that include putative high‐affinity ligands for E‐selectin. The N ‐glycans were prepared starting from a sialoglycopeptide isolated from egg yolk powder and took advantage of inherent substrate preferences of glycosyltransferases and the use of 5′‐diphospho‐ N ‐trifluoracetylglucosamine (UDP‐GlcNHTFA) that can be transferred by branching N ‐acetylglucosaminyltransferases to give, after base treatment, GlcNH 2 ‐containing glycans that temporarily disable an antenna from enzymatic modification. Glycan microarray binding studies showed that E‐selectin bound equally well to linear glycans and tri‐antennary N ‐glycans presenting SLe x ‐Le x . On the other hand, it was found that hemagglutinins (HA) of H5 influenza A viruses (IAV) preferentially bound the tri‐antennary N ‐glycans. Furthermore, several H5 HAs preferentially bound to N ‐glycan presenting SLe x on the MGAT4 arm. SLe x is displayed in the respiratory tract of several avian species, demonstrating the relevance of investigating the binding of, among others IAVs, to complex N ‐glycans presenting SLe x .","journal":"Chemistry - A European Journal","year":2024,"id":433856,"datarank":0.44588411592548227,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.05002551648319334,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.05002551648319334,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":998283,"name":"Cindy M. Spruit","orcid":"0000-0001-6570-7910","position":1,"is_corresponding":false},{"id":333692,"name":"Na Wei","orcid":"0000-0003-2093-3441","position":2,"is_corresponding":false},{"id":53124,"name":"Lin Liu","orcid":"0000-0002-0310-5946","position":3,"is_corresponding":false},{"id":550755,"name":"Margreet A. Wolfert","orcid":"0000-0003-4864-0026","position":4,"is_corresponding":false},{"id":472820,"name":"Robert P. de Vries","orcid":"0000-0002-1586-4464","position":5,"is_corresponding":false},{"id":53134,"name":"Geert‐Jan Boons","orcid":"0000-0003-3111-5954","position":6,"is_corresponding":false},{"id":547032,"name":"Tiehai Li","orcid":"0000-0002-3600-1828","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:49.434790Z","pmid":"38567703","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":[]}