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

Somovilla, V.J. ; Bermejo, I.A. ; Albuquerque, I.S. ; Martínez-Sáez, N. ; Castro-López, J. ; García-Martín, F. ; Compañón, I. ; Hinou, H. ; Nishimura, S.-I. ; Jiménez-Barbero, J. ; Asensio, J.L. ; Avenoza, A. ; Busto, J.H. ; Hurtado-Guerrero, R. (Universidad de Zaragoza) ; Peregrina, J.M. ; Bernardes, G.J.L. ; Corzana, F.

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)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B89
Financiación: info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2016-75633-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2013-44367-C2-2-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-64597-C2-1-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-67727-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/UNLR13-4E-1931

Tipo y forma: Article (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)