A team led by researchers from EPFL has developed a synthetic peptide-based method for detecting and measuring the protein calprotectin, a biomarker associated with inflammatory disorders like ulcerative colitis, Crohn's disease, and rheumatoid arthritis. Unlike traditional antibody-based assays, which can yield variable results, the peptide-based approach offers stability, cost-effectiveness, and high precision, according to the paper, which was published in Nature Communications.
The use of calprotectin as a diagnostic marker requires accurate quantification, and conventional antibody-based assays often suffer from inconsistencies due to variations in antibody composition and potential inactivation over time. In contrast, peptides, which are short amino acid sequences, can be chemically synthesized with high purity and uniformity. Peptides also offer greater stability, lower inter-batch variability, and cost advantages compared to antibodies.
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To develop the peptide-based method, the research team utilized a library of over 500 billion peptides. Cristina Diaz-Perlas, first author of the paper, isolated several peptides that bound to calprotectin with high affinity, demonstrating their suitability for quantifying calprotectin in simplified lateral flow assays. The most promising peptide exhibited a dissociation constant of 26 nM, indicating a strong binding affinity for calprotectin and making it an ideal candidate for diagnostic tests.
The unique peptide not only binds to a large surface region of calprotectin but also targets a specific form of the protein found in patient samples. The peptide was further tested in lateral flow cassettes, confirming its accuracy in detecting and quantifying calprotectin. In a proof-of-concept study, the peptide-based assay successfully measured calprotectin concentrations in serum obtained from patient blood samples.
This development is reportedly the first synthetic affinity reagent generated against the calprotectin biomarker. The researchers are now conducting further tests using the calprotectin-specific peptide to refine the assay and translate it into a commercial product. Their goal is to harness the diagnostic power of this increasingly important biomarker, enabling improved monitoring and diagnosis of patients with inflammatory diseases.