The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer

  1. Somovilla, V.J. 23
  2. Bermejo, I.A. 2
  3. Albuquerque, I.S. 10
  4. Martínez-Sáez, N. 23
  5. Castro-López, J. 9
  6. García-Martín, F. 7
  7. Compañón, I. 2
  8. Hinou, H. 7
  9. Nishimura, S.-I. 7
  10. Jiménez-Barbero, J. 158
  11. Asensio, J.L. 11
  12. Avenoza, A. 2
  13. Busto, J.H. 2
  14. Hurtado-Guerrero, R. 69
  15. Peregrina, J.M. 2
  16. Bernardes, G.J.L. 410
  17. Corzana, F. 2
  1. 1 Centro de Investigación Cooperativa en Biotecnología
    info

    Centro de Investigación Cooperativa en Biotecnología

    Zamudio, España

  2. 2 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  3. 3 Utrecht University
    info

    Utrecht University

    Utrecht, Holanda

    ROR https://ror.org/04pp8hn57

  4. 4 University of Cambridge
    info

    University of Cambridge

    Cambridge, Reino Unido

    ROR https://ror.org/013meh722

  5. 5 Universidad del País Vasco/Euskal Herriko Unibertsitatea
    info

    Universidad del País Vasco/Euskal Herriko Unibertsitatea

    Lejona, España

    ROR https://ror.org/000xsnr85

  6. 6 Fundación ARAID, Zaragoza, Spain
  7. 7 Hokkaido University
    info

    Hokkaido University

    Sapporo, Japón

    ROR https://ror.org/02e16g702

  8. 8 Ikerbasque, Fundación Vasca para la Ciencia
    info

    Ikerbasque, Fundación Vasca para la Ciencia

    Bilbao, España

    ROR https://ror.org/01cc3fy72

  9. 9 Universidad de Zaragoza
    info

    Universidad de Zaragoza

    Zaragoza, España

    ROR https://ror.org/012a91z28

  10. 10 Universidade de Lisboa
    info

    Universidade de Lisboa

    Lisboa, Portugal

    ROR https://ror.org/01c27hj86

  11. 11 Instituto de Química Orgánica General
    info

    Instituto de Química Orgánica General

    Madrid, España

    ROR https://ror.org/05e0q7s59

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Revue:
Journal of the American Chemical Society

ISSN: 0002-7863

Année de publication: 2017

Volumen: 139

Número: 50

Pages: 18255-18261

Type: Article

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DOI: 10.1021/JACS.7B09447 SCOPUS: 2-s2.0-85038620553 WoS: WOS:000418783600025 GOOGLE SCHOLAR

D'autres publications dans: Journal of the American Chemical Society

Dépôt institutionnel: lock_openAccès ouvert Editor

Objectifs de Développement Durable

Projets liés

Diseño estructural de glicopeptidos de tipo mucina que incorporan miméticos del antigeno TN para desarrollar biomarcadores y vacunas contra el cáncer.

2016/00001/001

Résumé

A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for prostate cancer. © 2017 American Chemical Society.