Design and synthesis of an acid-stable phosphoarginine mimetic retaining the α-amino acid structure

Abstract

Protein phosphorylation is a prevalent and crucial post-translational modification (PTM) of proteins. Although the use of phosphorylated amino acids as building blocks has become essential for studying phosphorylated target proteins, N-phosphorylated amino acids remain less explored because of their acid-labile Nsingle bondP bonds. Analogs with Nsingle bondP bonds replaced by Csingle bondP bonds are available for pLys and pHis, retaining the α-amino acid moiety. However, a similar acid-stable pArg mimetic has not been developed. This study introduces the synthesis of an acid-stable iminoethylphosphonic acid-containing pArg mimetic with α-amino acid moiety. The α-amino acid moiety is expected to allow the developed pArg mimetic to be specifically incorporated into peptides and proteins at targeted sites with a designed amino acid sequence.