{"doi":"10.1002/anie.202411863","title":"Enzymatic Synthesis of Disialyllacto‐<i>N</i>‐Tetraose (DSLNT) and Related Human Milk Oligosaccharides Reveals Broad Siglec Recognition of the Atypical Neu5Acα2‐6GlcNAc Motif","abstract":"Sialic acids (Sias) are ubiquitously expressed on all types of glycans, typically as terminating residues. They usually link to galactose, N-acetylgalactosamine, or other Sia residues, forming ligands of many glycan-binding proteins. An atypical linkage to the C6 of N-acetylglucosamine (GlcNAc) has been identified in human milk oligosaccharides (HMOs, e.g., DSLNT) and tumor-associated glycoconjugates. Herein, describe the systematic synthesis of these HMOs in an enzymatic modular manner. The synthetic strategy relies on a novel activity of ST6GalNAc6 for efficient construction of the Neu5Acα2-6GlcNAc linkage, and another 12 specific enzyme modules for sequential HMO assembly. The structures enabled comprehensive exploration of their structure-function relationships using glycan microarrays, revealing broad yet distinct recognition by Siglecs of the atypical Neu5Acα2-6GlcNAc motif. The work provides tools and new insight for the functional study and potential applications of Siglecs and HMOs.","journal":"Angewandte Chemie International Edition","year":2024,"id":425672,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"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":1224429,"name":"Tangliang Shen","orcid":null,"position":1,"is_corresponding":false},{"id":1224430,"name":"MohammadHossein Shabahang","orcid":null,"position":2,"is_corresponding":false},{"id":1224431,"name":"Guitao Bai","orcid":null,"position":3,"is_corresponding":false},{"id":374916,"name":"Lei Li","orcid":"0000-0002-1146-0761","position":4,"is_corresponding":false},{"id":1051764,"name":"Shumin Bao","orcid":"0009-0006-7512-8799","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:32.160975Z","pmid":"39223086","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":[]}