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