Designed Glucopeptides
Mimetics of Myelin Protein Epitopes As Synthetic Probes for the Detection
of Autoantibodies, Biomarkers of Multiple Sclerosis
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Abstract
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’ 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’ sera may be
ascribed to both the optimized design of its epitopic region and the
superior surface interacting properties of its C-terminal region