The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer
- Somovilla, V.J. 23
- Bermejo, I.A. 2
- Albuquerque, I.S. 10
- Martínez-Sáez, N. 23
- Castro-López, J. 9
- García-Martín, F. 7
- Compañón, I. 2
- Hinou, H. 7
- Nishimura, S.-I. 7
- Jiménez-Barbero, J. 158
- Asensio, J.L. 11
- Avenoza, A. 2
- Busto, J.H. 2
- Hurtado-Guerrero, R. 69
- Peregrina, J.M. 2
- Bernardes, G.J.L. 410
- Corzana, F. 2
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1
Centro de Investigación Cooperativa en Biotecnología
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Centro de Investigación Cooperativa en Biotecnología
Zamudio, España
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2
Universidad de La Rioja
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3
Utrecht University
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4
University of Cambridge
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5
Universidad del País Vasco/Euskal Herriko Unibertsitatea
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Universidad del País Vasco/Euskal Herriko Unibertsitatea
Lejona, España
- 6 Fundación ARAID, Zaragoza, Spain
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7
Hokkaido University
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8
Ikerbasque, Fundación Vasca para la Ciencia
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9
Universidad de Zaragoza
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10
Universidade de Lisboa
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11
Instituto de Química Orgánica General
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ISSN: 0002-7863
Año de publicación: 2017
Volumen: 139
Número: 50
Páginas: 18255-18261
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Journal of the American Chemical Society
Proyectos relacionados
Resumen
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.