Projects / Autoimmune mediate diseases / Primary Biliary Cirrhosis

Synthesis of diastereoisomeric modified amino acids derived from alpha-lipoic acid for use in solid phase peptide synthesis

Profiles

In collaboration with:

University of Milan Clinical Immunology, Humanitas Clinical and Research Center and University of California, Davis

Carlo Selmi

The use of synthetic post-translationally modified peptides, introducing Fmoc-L-Lys(Nepsilon-(±)-alpha-Lipoic acid)-OH, as peptidomimetics of natural neoantigens allowed to detect autoantibodies in the sera of patients affected by PBC, and they might be useful diagnostic tools that can be used in earlier stage patients and possibly to monitor disease activity. Only the R-(+)-enantiomer of alpha-lipoic acid exists in nature and is an essential cofactor of four mitochondrial enzyme complexes. But it remains unclear if the tridimensional structure of the lipoic acid is of any importance in the interactions antibody-peptide during the indirect ELISA tests. Therefore, teh necessisty to synthesize each peptide separately with one absolute configuration of the lipoic acid. Aim of this research project is the synthesis of the two diastereoisomers Fmoc-L-Lys(Nepsilon-(R)-alpha-Lipoic acid)-OH and Fmoc-L-Lys(Nepsilon-(S)-alpha-Lipoic acid)-OH that have to be used in Fmoc/tBu SPPS as building blocks for the synthesis of post-translationally modified peptides.

 

 

 

 

 

 

 

 

 

 

 

 

Scheme: Synthetic pathway to N6-(1,2-dithiolane-(3R)-pentanoyl)-N2-Fmoc-L-Lys-OH.

 

 

Poster presentation

Synthesis of diastereoisomeric modified amino acids derived from alpha-lipoic acid for use in solid phase peptide synthesis. C. Rentier, F. Nuti, G.  Pacini, P. Rovero, C. Selmi, and A. M. Papini 32 European Peptide Symposium, 2-7 Settembre 2012 Atene, Greece