Deciphering the Non-Equivalence of Serine and Threonine O-glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody

  1. Martínez-Sáez, N. 24
  2. Castro-Lõpez, J. 57
  3. Valero-González, J. 57
  4. Madariaga, D. 2
  5. Compañõn, I. 2
  6. Somovilla, V.J. 24
  7. Salvadó, Mirian. 14
  8. Asensio, J.L. 9
  9. Jiménez-Barbero, J. 3610
  10. Avenoza, A. 2
  11. Busto, J.H. 2
  12. Bernardes, G.J.L. 48
  13. Peregrina, J.M. 2
  14. Hurtado-Guerrero, R. 57
  15. Corzana, F. 2
  1. 1 Universitat Rovira i Virgili
    info

    Universitat Rovira i Virgili

    Tarragona, España

    ROR https://ror.org/00g5sqv46

  2. 2 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  3. 3 Centro de Investigaciones Biológicas
    info

    Centro de Investigaciones Biológicas

    Madrid, España

    ROR https://ror.org/04advdf21

  4. 4 University of Cambridge
    info

    University of Cambridge

    Cambridge, Reino Unido

    ROR https://ror.org/013meh722

  5. 5 Fundaciõn ARAID, Edificio Pignatelli 36, Zaragoza, Spain
  6. 6 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
  7. 7 Universidad de Zaragoza
    info

    Universidad de Zaragoza

    Zaragoza, España

    ROR https://ror.org/012a91z28

  8. 8 Universidade de Lisboa
    info

    Universidade de Lisboa

    Lisboa, Portugal

    ROR https://ror.org/01c27hj86

  9. 9 Instituto de Química Orgánica General
    info

    Instituto de Química Orgánica General

    Madrid, España

    ROR https://ror.org/05e0q7s59

  10. 10 Centro de Investigación Cooperativa en Biotecnología
    info

    Centro de Investigación Cooperativa en Biotecnología

    Zamudio, España

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Zeitschrift:
Angewandte Chemie International

ISSN: 1433-7851

Datum der Publikation: 2015

Ausgabe: 54

Nummer: 34

Seiten: 9830

Art: Artikel

DOI: 10.1002/ANIE.201502813 SCOPUS: 2-s2.0-84939000734 WoS: WOS:000360215100009 GOOGLE SCHOLAR

Andere Publikationen in: Angewandte Chemie International

Ziele für nachhaltige Entwicklung

Zusammenfassung

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. © 2015 The Authors.