{"doi":"10.1101/2020.12.13.422539","title":"Efficient Inhibition of O-glycan biosynthesis using the hexosamine analog Ac <sub>5</sub> GalNTGc","abstract":"SUMMARY There is a critical need to develop small molecule inhibitors of mucin-type O-linked glycosylation. The best known reagent currently is peracetylated benzyl-GalNAc, but it is only effective at millimolar concentrations. This manuscript demonstrates that Ac 5 GalNTGc, a peracetylated C-2 sulfhydryl substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast and prostate cells, Ac 5 GalNTGc increased cell surface VVA-binding by ~10-fold, indicating truncation of O-glycan biosynthesis. Cytometry, mass spectrometry and Western blot analysis of HL-60 promyelocytes demonstrate that 50-80μM Ac 5 GalNTGc prevented elaboration of 30-60% of the O-glycans beyond the Tn-antigen (GalNAcα1-Ser/Thr) stage. The effect of the compound on N-glycans and glycosphingolipids was small. Glycan inhibition induced by Ac 5 GalNTGc resulted in 50-80% reduction in leukocyte sialyl-Lewis-X expression, and L-/P-selectin mediated rolling under flow. Ac 5 GalNTGc was pharmacologically active in mouse. It reduced neutrophil infiltration to sites of inflammation by ~60%. Overall, Ac 5 GalNTGc may find diverse applications as a potent inhibitor of O-glycosylation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125693,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396754,"name":"Virginia del Solar","orcid":"0000-0001-9405-674X","position":1,"is_corresponding":false},{"id":241856,"name":"Xinheng Yu","orcid":"0000-0002-7204-6476","position":2,"is_corresponding":false},{"id":288033,"name":"Aristotelis Antonopoulos","orcid":"0000-0002-1592-4092","position":3,"is_corresponding":false},{"id":503560,"name":"Alan E. Friedman","orcid":"0000-0002-4764-8168","position":4,"is_corresponding":false},{"id":572458,"name":"Kavita Agarwal","orcid":"0000-0002-6472-0731","position":5,"is_corresponding":false},{"id":572459,"name":"Monika Garg","orcid":"0000-0002-2297-1137","position":6,"is_corresponding":false},{"id":573135,"name":"Syed Meheboob Ahmed","orcid":null,"position":7,"is_corresponding":false},{"id":573136,"name":"Ahana Addhya","orcid":null,"position":8,"is_corresponding":false},{"id":572460,"name":"Mehrab Nasirikenari","orcid":"0000-0001-5267-3395","position":9,"is_corresponding":false},{"id":319757,"name":"Joseph T.Y. Lau","orcid":"0000-0002-5128-2664","position":10,"is_corresponding":false},{"id":471337,"name":"Anne Dell","orcid":"0000-0003-1380-2347","position":11,"is_corresponding":false},{"id":288040,"name":"Stuart M. Haslam","orcid":"0000-0002-5563-679X","position":12,"is_corresponding":false},{"id":572461,"name":"Srinivasa‐Gopalan Sampathkumar","orcid":"0000-0002-0616-8977","position":13,"is_corresponding":false},{"id":241859,"name":"Sriram Neelamegham","orcid":"0000-0002-1371-8500","position":14,"is_corresponding":false},{"id":573134,"name":"Shuen-Shiuan Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:15:19.482428Z","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":[]}