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The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer
- Somovilla, Víctor J., Bermejo, Iris A., Albuquerque, Inês S., Martínez-Sáez, Nuria, Castro-López, Jorge, García-Martín, Fayna, Compañón, Ismael, Hinou, Hiroshi, Nishimura, Shin-Ichiro, Jiménez-Barbero, Jesús, Asensio, Juan L., Avenoza, Alberto, Busto, Jesús H., Hurtado-Guerrero, Ramón, Peregrina, Jesús M., Bernardes, Gonçalo J. L., Corzana, Francisco
- Journal of the American Chemical Society 2017 v.139 no.50 pp. 18255-18261
- X-ray diffraction, antibodies, antigen-antibody complex, antigens, blood serum, diagnostic techniques, glycopeptides, interferometry, patients, proline, prostatic neoplasms
- 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.