Design of α-S-Neoglycopeptides Derived from MUC1 with a Flexible and Solvent-Exposed Sugar Moiety

  1. Rojas-Ocáriz, V. 3
  2. Compañón, I. 3
  3. Aydillo, C. 23
  4. Castro-Loṕez, J. 1
  5. Jiménez-Barbero, J. 46
  6. Hurtado-Guerrero, R. 15
  7. Avenoza, A. 3
  8. Zurbano, M.M. 3
  9. Peregrina, J.M. 3
  10. Busto, J.H. 3
  11. Corzana, F. 3
  1. 1 Universidad de Zaragoza
    info
    Universidad de Zaragoza

    Zaragoza, España

    ROR https://ror.org/012a91z28

    Erakundearen kokapen geografikoa Universidad de Zaragoza
  2. 2 University of Copenhagen
    info
    University of Copenhagen

    Copenhague, Dinamarca

    ROR https://ror.org/035b05819

    Erakundearen kokapen geografikoa University of Copenhagen
  3. 3 Universidad de La Rioja
    info
    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

    Erakundearen kokapen geografikoa Universidad de La Rioja
  4. 4 Centro de Investigaciones Biológicas
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    Centro de Investigaciones Biológicas

    Madrid, España

    ROR https://ror.org/04advdf21

    Erakundearen kokapen geografikoa Centro de Investigaciones Biológicas
  5. 5 Fundación Agencia Aragonesa para la Investigación y el Desarrollo
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    Fundación Agencia Aragonesa para la Investigación y el Desarrollo

    Zaragoza, España

    Erakundearen kokapen geografikoa Fundación Agencia Aragonesa para la Investigación y el Desarrollo
  6. 6 Ikerbasque, Fundación Vasca para la Ciencia
    info
    Ikerbasque, Fundación Vasca para la Ciencia

    Bilbao, España

    ROR https://ror.org/01cc3fy72

    Erakundearen kokapen geografikoa Ikerbasque, Fundación Vasca para la Ciencia
Erakutsi afiliazioak +
Aldizkaria:
Journal of Organic Chemistry

ISSN: 0022-3263

Argitalpen urtea: 2016

Alea: 81

Zenbakia: 14

Orrialdeak: 5929-5941

Mota: Artikulua

DOI: 10.1021/ACS.JOC.6B00833 SCOPUS: 2-s2.0-84978517876 WoS: WOS:000380181500013 GOOGLE SCHOLAR

Beste argitalpen batzuk: Journal of Organic Chemistry

Garapen Iraunkorreko Helburuak

Laburpena

The use of vaccines based on MUC1 glycopeptides is a promising approach to treat cancer. We present herein several sulfa-Tn antigens incorporated in MUC1 sequences that possess a variable linker between the carbohydrate (GalNAc) and the peptide backbone. The main conformations of these molecules in solution have been evaluated by combining NMR experiments and molecular dynamics simulations. The linker plays a key role in the modulation of the conformation of these compounds at different levels, blocking a direct contact between the sugar moiety and the backbone, promoting a helix-like conformation for the glycosylated residue and favoring the proper presentation of the sugar unit for molecular recognition events. The feasibility of these novel compounds as mimics of MUC1 antigens has been validated by the X-ray diffraction structure of one of these unnatural derivatives complexed to an anti-MUC1 monoclonal antibody. These features, together with potential lack of immune suppression, render these unnatural glycopeptides promising candidates for designing alternative therapeutic vaccines against cancer. © 2016 American Chemical Society.