biostudies-literatureYang YNational Institutes of HealthNIGMS NIH HHSe202300081https://www.ebi.ac.uk/biostudies/studies/S-EPMC11081099biostudies-literatureUnknown63(10-11)Truncated mucin-type O-glycans, such as Tn-associated antigens, are aberrantly expressed biomarkers of cancer, but remain challenging to target. Reactive antibodies to these antigens either lack high-affinity or are prone to antigen escape. Here, we have developed a robust chemoenzymatic strategy for the global labeling of Tn-associated antigens, i.e. Tn (GalNAcα-O-Ser/Thr), Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, TF) and STF (Neu5Acα2-3Galβ1-3GalNAcα-O-Ser/Thr, STF) antigens, in human whole blood with high efficiency and selectivity. This method relies on the use of the O-glycan sialyltransferase ST6GalNAc1 to transfer a sialic acid-functionalized adaptor to the GalNAc residue of these antigens. By tagging, the adaptor functionalized antigens can be easily targeted by customized sIsrael journal of chemistryChemoenzymatic Tagging of Tn/TF/STF Antigens in Living Systems.PMC11081099P41 GM103390R35 GM139643P01GM107012R01GM117145R01 GM130915U01 GM120408U01GM120408R01GM130915P01 GM107012P41 GM103390R01 GM117145R35GM139643Yang JYGao BSharpless KBWu MChen MYoung TSChapla DGWu PCappiello JRMoremen KWLiu YYang YYu CLi JPHong SfalseChemoenzymatic Tagging of Tn/TF/STF Antigens in Living Systems.Truncated mucin-type O-glycans, such as Tn-associated antigens, are aberrantly expressed biomarkers of cancer, but remain challenging to target. Reactive antibodies to these antigens either lack high-affinity or are prone to antigen escape. Here, we have developed a robust chemoenzymatic strategy for the global labeling of Tn-associated antigens, i.e. Tn (GalNAcα-O-Ser/Thr), Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, TF) and STF (Neu5Acα2-3Galβ1-3GalNAcα-O-Ser/Thr, STF) antigens, in human whole blood with high efficiency and selectivity. This method relies on the use of the O-glycan sialyltransferase ST6GalNAc1 to transfer a sialic acid-functionalized adaptor to the GalNAc residue of these antigens. By tagging, the adaptor functionalized antigens can be easily targeted by customized s2023-01-01T00:00:00Z2023 Oct2025-04-04T01:03:21.056Z2025-04-04T01:03:21.056ZS-EPMC110810993873767010.1002/ijch.202300081