The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer
Financiación FP7 / Fp7 Funds
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)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.


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