Synthesis of diastereomerically pure Lys(Nε‐lipoyl) building blocks and their use in Fmoc/tBu solid phase synthesis of lipoyl‐containing peptides for diagnosis of primary biliary cirrhosis1. (26th March 2015)

• Record Type: Journal Article
• Authors: Rentier, Cédric; Pacini, Giulia; Nuti, Francesca; Peroni, Elisa; Rovero, Paolo; Papini, Anna Maria; Morelli, Giancarlo
• Is Part Of: Journal of peptide science. Volume 21:Number 5(2015:May)
• Page Start: 408
• Page End: 414
• Publication Date: 2015-03-26
• Subjects: Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2761
• Languages: English
• ISSNs: 1075-2617

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Primary Biliary Cirrhosis is an immune‐mediated disease in which one of the epitopes recognized by antimitochondrial autoantibodies is a lipoylated fragment of the PDC‐E2 protein. Accordingly, the synthesis of lipoylated peptides as diagnostic tools is a relevant target. Up to now, the proper tools for the introduction of lipoylation on building blocks to be used in Fmoc/tBu solid phase peptide synthesis (SPPS) are lacking, and the role of chirality in lipoylation remains poorly studied.</p> <p>In this paper, we present the synthesis of lipoylated lysine derivatives as pure diastereomeric building blocks suitable for Fmoc/tBu SPPS and their introduction in relevant peptide sequences to possibly serve as synthetic probes for the development of novel diagnostic tools for this disease.</p> <p>The optimization of the synthesis of lipoylated building blocks derived from racemic, (<italic>R</italic>)‐, and (<italic>S</italic>)‐α‐lipoic acid is described. Synthesis of peptide probes incorporating lipoylation is described. An insight regarding the cleavage of lipoylated peptides is given, as well as a method to oxidize or reduce the 1, 2‐dithiolane ring of the lipoyl moiety directly on the peptide without any subsequent purification. Copyright © 2015 European Peptide Society and John Wiley &amp; Sons, Ltd.</p> </abstract>