Designed Glucopeptides Mimetics of Myelin Protein Epitopes As Synthetic Probes for the Detection of Autoantibodies, Biomarkers of Multiple Sclerosis

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• 作者：Shashank Pandey ; Maria C. Alcaro ; Mario Scrima ; Elisa Peroni ; Ilaria Paolini ; Sara Di Marino ; Francesca Barbetti ; Alfonso Carotenuto ; Ettore Novellino ; Anna Maria Papini ; Anna Maria D鈥橴rsi ; Paolo Rovero
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：55
• 期：23
• 页码：10437-10447
• 全文大小：422K
• 年卷期：v.55,no.23(December 13, 2012)
• ISSN：1520-4804

文摘

We previously reported that CSF114(Glc) detects diagnostic autoantibodies in multiple sclerosis sera. We report herein a bioinformatic analysis of myelin proteins and CSF114(Glc), which led to the identification of five sequences. These glucopeptides were synthesized and tested in enzymatic assays, showing a common minimal epitope. Starting from that, we designed an optimized sequence, SP077, showing a higher homology with both CSF114(Glc) and the five sequences selected using the bioinformatic approach. SP077 was synthesized and tested on 50 multiple sclerosis patients鈥?sera, and was able to detect higher antibody titers as compared to CSF114(Glc). Finally, the conformational properties of SP077 were studied by NMR spectroscopy and structure calculations. Thus, the immunological activity of SP077 in the recognition of specific autoantibodies in multiple sclerosis patients鈥?sera may be ascribed to both the optimized design of its epitopic region and the superior surface interacting properties of its C-terminal region.