In:
Angewandte Chemie International Edition, Wiley, Vol. 54, No. 34 ( 2015-08-17), p. 9830-9834
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.
Type of Medium:
Online Resource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.201502813
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2011836-3
detail.hit.zdb_id:
123227-7
Permalink