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/p 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. Idioma: Inglés DOI: 10.1021/jacs.7b09447 Año: 2017 Publicado en: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139, 50 (2017), 18255-18261 ISSN: 0002-7863 Factor impacto JCR: 14.357 (2017) Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 8 / 171 = 0.047 (2017) - Q1 - T1 Factor impacto SCIMAGO: 8.127 - Biochemistry (Q1) - Colloid and Surface Chemistry (Q1) - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)