Projects / Autoimmune mediate diseases / Multiple Sclerosis

beta-Turns and bioinformatic approach for Multiple Sclerosis diagnostics development

Profiles

 

In collaboration with:

Department of Pharmaceutical and Toxicological Chemistry, University of Naples ‘‘Federico II,’’  Naples, Italy

Ettore Novellino and alfonso Carotenuto

Department of Pharmaceutical Sciences, University of Salerno, Italy

Anna Maria D'Ursi

Toscana Biomarkers Srl, Siena, Italy

Maria C. Alcaro, Ilaria Paolini and Francesca Barbetti

In the field of diagnostics The PeptLab team is involved in developing peptides as tools for the detection of biomarkers in autoimmune diseases contributing to an early diagnosis, a better prognosis, and optimized therapy. In fact synthetic peptides represent a ideal antigenic target for immunoassays because they can be produced in high quality and can be characterized by a precise and definite chemical sequence. Moreover peptides can be used to introduce specific post translational modifications or to stabilize the bioactive conformation. In particular, we previously demonstrated the ability of glycopeptides that bear the minimal epitope Asn(Glc) to detect autoantibodies in multiple sclerosis (MS) patients but not in healthy controls by using solid-phase ELISA. A conformation-activity relationship study of these glycopeptides revealed the role of conformation both in antibody recognition and binding of MS autoantibodies in the solid-phase context of the immunoenzymatic assay. In particular, all glycopeptides that revealed high antibody titers in MS sera showed a type I’ beta-turn around the minimal epitope Asn(Glc), because of an efficient exposure of this moiety to autoantibody interaction in the solid phase conditions of the ELISA. With the aim of optimizing the glycopeptide-antibody interactions in multiple sclerosis, we designed, synthesized, and analyzed a series of  glycopeptides based on different beta-turn structures. 

Our studies confirmed for the first time the role of the peptide sequence and of the β-turn conformation in the recognition and binding of synthetic antigenic probes to MS autoantibodies in the context of the immunoenzymatic assay e.g. the ELISA. We performed both a sequence and a 3D alignment study of myelin proteins and the glucosylated beta-turn peptide. The homology results were instrumental for the design of a second generation of optimized antigenic probes.