Synthesis of diastereomeric building-blocks of lipoylated-Lysine and their use in SPPS.

Primary Biliary Cirrhosis (PBC) is an autoimmune liver disease, in which intrahepatic bile ducts are progressively destroyed leading to bile accumulation, cirrhosis, and liver failure in the later stages of the disease [1]. Antimitochondrial autoantibodies (AMA) present in > 90% patients’ sera are claimed to recognize a lipoylated inner domain of the E2 component of the pyruvate dehydrogenase complex (PDC-E2) and are relevant for the disease [2]. Nevertheless the role of the lipoyl moiety in antibody recognition has not been yet completely clarified. Lipoylation consists of a lipoic acid linked to the Lys side chain via an amide bond. The present study reports the first synthesis of diastereomerically pure lipoylated-Lysine building blocks and their introduction in relevant peptide sequences to be used as molecular probes for PBC diagnostics.