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)

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 Record created 2018-02-15, last modified 2019-07-09

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