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

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journal contribution
posted on 22.11.2017 by Víctor J. Somovilla, Iris A. Bermejo, Inês S. Albuquerque, Nuria Martínez-Sáez, Jorge Castro-López, Fayna García-Martín, Ismael Compañón, Hiroshi Hinou, Shin-Ichiro Nishimura, Jesús Jiménez-Barbero, Juan L. Asensio, Alberto Avenoza, Jesús H. Busto, Ramón Hurtado-Guerrero, Jesús M. Peregrina, Gonçalo J. L. Bernardes, Francisco Corzana
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.