Abstract
The structural features of MUC1-like glycopeptides bearing the Tn antigen (α-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the α-O-GalNAc-Ser derivative, the glycosidic linkage adopts a high-energy conformation, barely populated in the free state. This unusual structure (also observed in an α-S-GalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies.
Highlights
The structural features of MUC1-like glycopeptides bearing the Tn antigen (a-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution
The selection of a particular peptide structure by the antibody is propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the a-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group
The similar to that of other anti-MUC1 antibodies,[24] which overall conformation of the peptide fragment of the different expands the scope of these results, and because of its simplified MUC1 variants is nearly identical and is similar to potential for use in the early diagnosis and treatment of breast that found in the crystal structure reported for the naked cancer.[22]
Summary
Abstract: The structural features of MUC1-like glycopeptides bearing the Tn antigen (a-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. The Ser-To our knowledge, the only reported crystal structure of containing compounds showed significantly lower affinity, a complex between an antibody and a GalNAc-containing highlighting the differences between the two Tn antigens.
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