Synthetic Approach to Argpyrimidine as a Tool for Investigating Nonenzymatic Posttranslational Modification of ProteinsSupported by: Austrian Academy of Sciences (APART fellowship)
Received: 24 January 2017
Accepted after revision: 12 March 2017
19 April 2017 (eFirst)
Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis
Nonenzymatic posttranslational modifications (nPTMs) of proteins are involved in age-related, metabolic and other diseases and need to be investigated at the molecular level. Here, we describe how we used organic synthesis to enable the study of the effect of argpyrimidine (Apy), an nPTM that forms at arginine residues, on one of its target proteins. We developed an efficient approach to Apy as a universal building block for Fmoc-based solid-phase peptide synthesis that allows for the construction of peptides containing this nPTM in predetermined positions. Moreover, a straightforward one-step synthesis of protecting-group-free Apy was achieved, which enabled the preparation of gram-quantities of this noncanonical amino acid that can serve as a biomarker or a feedstock in construction of Apy-containing proteins via the expanded genetic code methods.