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

DOI: 10.1021/jacs.7b09447 DOI Help

Authors: Víctor Jesús Somovilla (Universidad de La Rioja; Utrecht Institute for Pharmaceutical Sciences) , Iris Alicia Bermejo (Universidad de La Rioja) , Inês S. Albuquerque (Universidade de Lisboa) , Nuria Martínez-Sáez (Universidad de La Rioja; Utrecht Institute for Pharmaceutical Sciences) , Jorge Castro-López (University of Zaragoza) , Fayna Garcia Martin (Hokkaido University) , Ismael Compañón (Universidad de La Rioja) , Hiroshi Hinou (Hokkaido University) , Shin-Ichiro Nishimura (Hokkaido University) , Jesús Jiménez-Barbero (CIC bioGUNE) , Juan Luis Asensio (Instituto de Química Orgánica General) , Alberto Avenoza (Universidad de La Rioja) , Jesús H Busto (Universidad de La Rioja) , Ramon Hurtado-Guerrero (University of Zaragoza; Fundación ARAID) , Jesús M. Peregrina (Universidad de La Rioja) , Gonçalo J.l. Bernardes (Universidade de Lisboa; University of Cambridge) , Francisco Corzana (Universidad de La Rioja)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society

State: Published (Approved)
Published: November 2017
Diamond Proposal Number(s): 10121

Open Access Open Access

Abstract: A structure-based design of a new generation 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/π 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.

Journal Keywords: Immunology; Peptides and proteins; Monomers; Antigens; Biopolymers

Diamond Keywords: Prostate Cancer

Subject Areas: Chemistry, Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography

Added On: 11/12/2017 09:28

Documents:
ja5656cs.pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)