CUED Publications database

The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer

Somovilla, VJ and Bermejo, IA and Albuquerque, IS and Martínez-Sáez, N and Castro-López, J and García-Martín, F and Compañón, I and Hinou, H and Nishimura, S and Jiménez-Barbero, J and Asensio, JL and Avenoza, A and Busto,, JH and Hurtado-Guerrero, R and Peregrina, JM and Lopes Bernardes, GJ and Corzana1, F (2017) The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer. Journal of the American Chemical Society, 139. pp. 18255-18261.

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Abstract

A structure-based design of a new gene22ration 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-difluoroproline, at the most immunogenic domain. Binding assays using bio-layer 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/ 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 this type of cancer.

Item Type: Article
Uncontrolled Keywords: Amino Acid Sequence Antibodies Binding Sites, Antibody Crystallography, X-Ray Drug Design Humans Molecular Dynamics Simulation Mucin-1 Peptides Proline
Subjects: UNSPECIFIED
Divisions: UNSPECIFIED
Depositing User: Cron Job
Date Deposited: 25 Jun 2019 02:49
Last Modified: 10 Apr 2021 22:48
DOI: 10.1021/jacs.7b09447