2023-05-17 スイス連邦工科大学ローザンヌ校(EPFL)
◆炎症性疾患の診断や経過観察にはカルプロテクチンの測定が重要であり、このペプチドは診断テストにおいて有望な候補となっています。今後の研究では、ペプチドを用いた試験を製品化し、炎症性疾患を抱える患者の診断に貢献することが期待されています。
◆この研究は、抗体とは異なるアプローチで疾患マーカーを検出する可能性を示し、医療診断の改善に向けた新たな展望を開いています。
<関連情報>
- https://actu.epfl.ch/news/diagnosing-inflammatory-diseases-with-synthetic-pe/
- https://www.nature.com/articles/s41467-023-38075-7
カルプロテクチンに対して開発された高親和性ペプチドと、診断アッセイにおける合成リガンドとしてのその応用 High-affinity peptides developed against calprotectin and their application as synthetic ligands in diagnostic assays
Cristina Díaz-Perlas,Benjamin Ricken,Lluc Farrera-Soler,Dmitrii Guschin,Florence Pojer,Kelvin Lau,Christian-Benedikt Gerhold & Christian Heinis
Nature Communications Published:17 May 2023
DOI:https://doi.org/10.1038/s41467-023-38075-7
Abstract
Common inflammatory disorders such as ulcerative colitis and Crohn’s disease are non-invasively diagnosed or monitored by the biomarker calprotectin. However, current quantitative tests for calprotectin are antibody-based and vary depending on the type of antibody and assay used. Additionally, the binding epitopes of applied antibodies are not characterized by structures and for most antibodies it is unclear if they detect calprotectin dimer, tetramer, or both. Herein, we develop calprotectin ligands based on peptides, that offer advantages such as homogenous chemical composition, heat-stability, site-directed immobilization, and chemical synthesis at high purity and at low cost. By screening a 100-billion peptide phage display library against calprotectin, we identified a high-affinity peptide (Kd = 26 ± 3 nM) that binds to a large surface region (951 Å2) as shown by X-ray structure analysis. The peptide uniquely binds the calprotectin tetramer, which enabled robust and sensitive quantification of a defined species of calprotectin by ELISA and lateral flow assays in patient samples, and thus offers an ideal affinity reagent for next-generation inflammatory disease diagnostic assays.
