Ribose Building Block For The Synthesis Of Glycopeptides For Fishing Out Antibodies In Autoimmune Diseases

Introduction It is well known that ribose (Rib) is produced in vivo from glucose and it plays a fundamental role in cellular energy metabolism and cellular signaling. Mono (ADPribosyl)transferases transfer single ADP-ribose moieties to acceptor proteins. Following our hypothesis that an aberrant glucosylation triggers autoimmunity in Multiple Sclerosis (MS) (because of a bacterial or viral infection?), we can assume that a ribose moiety may be also transferred to protein components of organs or tissue target of autoimmune diseases. For the first time, by a structure-based design, we selected CSF114(Glc) as a synthetic glycopeptide, containing a β-glucosyl moiety linked to an Asparagine residue at position 7. CSF114(Glc) can be used as a specific Multiple Sclerosis Antigenic Probe (MSAP). We demonstrated that the glucosylasparagine Asn(Glc) is fundamental for autoantibody recognition in a form of MS [1]. In previous studies, we synthesized and tested in Enzyme-Linked Inmuno Sorbent Assay (ELISA) a large CSF114-type glycopeptide library based on N-glycosyl amino acid diversity (Glc, Man, GlcβGlc, Gal, GlcNAc, etc) and up to now, we have never investigated the role of ribose [2]. Considering that different families of autoantibodies to proteins aberrantly glycosylated with different sugar moieties could correlate with disease activity, we synthesized Fmoc-Asn(Rib)-OH. This building block will be introduced in the CSF114 β-turn scaffold to test this new ribosylated peptide as synthetic antigen contributing to the library of glycopeptides for fishing out families of autoantibodies specific for different forms of Multiple Sclerosis or other autoimmune diseases.