Chemical Synthesis of the Multiply Phosphorylated and Biotinylated N-Terminal Transactivation Domain of Human p53 (p53TAD)This material is based upon work supported by the National Science Foundation under CHE - 1454925.
Received: 30 April 2017
Accepted after revision: 17 June 2017
20 July 2017 (eFirst)
Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis
Phosphorylation of the N-terminal transactivation domain (TAD) of tumor suppressor p53 (p53TAD) helps regulate many of p53’s biological functions. Chemical synthesis of the p53TAD sequence with various phosphorylation patterns, through native chemical ligation and metal-free desulfurization, would facilitate studies of p53TAD phosphorylation and its role in regulating p53 function. Here, unphosphorylated, mono- and pentaphosphorylated p53TAD constructs were chemically synthesized. During the synthesis, methionine oxidation was found to be a serious problem and reduction was required at different stages, according to the number of phosphorylation sites.