Projects / Autoimmune mediate diseases / Diabetes

Synthesis of glycated and glycosylated peptides to detect autoantibodies in diabetic patients’ sera

Profiles

In collaboration with:

CNR ISTM, Padua, Italy

Piero Traldi

University of Padua, Dipartimento Sci. Med. & Chirurg., Padua, Italy

A Lapolla

Laboratory for Translational Research, Harvard Medical School and  Department of Medicine, Brigham and Women’s Hospital, Boston, USA

Michael Chorev

Diabetes is characterized by abnormal concentration of glucose in the blood (hyperglycemia). Among the existing mechanisms for post-translational modifications of proteins with sugars, we can underline two different ones: the non-enzymatic mechanism (i.e.,glycation) implying a reductive sugar (like glucose) and the free amino functions present in proteins leading to the formation of advanced glycation end-products (AGE), through the corresponding Schiff base rearranging into the more stable Amadori product, and the enzymatic mechanism (i.e., glycosylation), giving rise to N- or O-glycosylation patterns.

Pathways for AGEs formation

AGE are believed to play a role in many diabetic complications: retinopathy, nephropathy, neuropathy, cardiovascular complications or macrovascular cell proliferation.  We speculate that hyperglycemia may generate a higher concentration of glycated/glycosylated peptides in diabetic patients’ biological fluids compared to healthy individuals. Thus, we propose to use such post-translationally modified peptides as probes mimicking glycated and glycosylated neoantigens for the detection of autoantibodies in the sera of diabetic patients (types I and II) in indirect SP-ELISA. In particular, the CSF114(Glc), characterized by its b-hairpin, and the glycated analogue, obtained introducing the protected 1-deoxyfructopyranosyllysine as building-block ready for SPPS. We also report the results of currently under investigation MS/MS experiments on those peptides.